chr16-1519931-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014714.4(IFT140):​c.3990G>A​(p.Ala1330Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,600,638 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0048 ( 41 hom. )

Consequence

IFT140
NM_014714.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.37

Publications

1 publications found
Variant links:
Genes affected
IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]
IFT140 Gene-Disease associations (from GenCC):
  • autosomal dominant polycystic kidney disease
    Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
  • IFT140-related recessive ciliopathy
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
  • short-rib thoracic dysplasia 9 with or without polydactyly
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
  • retinitis pigmentosa 80
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
  • Leber congenital amaurosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • retinitis pigmentosa
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Jeune syndrome
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 16-1519931-C-T is Benign according to our data. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-5.37 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1650/152388) while in subpopulation AFR AF = 0.028 (1166/41592). AF 95% confidence interval is 0.0267. There are 12 homozygotes in GnomAd4. There are 771 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFT140NM_014714.4 linkc.3990G>A p.Ala1330Ala synonymous_variant Exon 29 of 31 ENST00000426508.7 NP_055529.2 Q96RY7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFT140ENST00000426508.7 linkc.3990G>A p.Ala1330Ala synonymous_variant Exon 29 of 31 5 NM_014714.4 ENSP00000406012.2 Q96RY7-1

Frequencies

GnomAD3 genomes
AF:
0.0108
AC:
1647
AN:
152270
Hom.:
13
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0280
Gnomad AMI
AF:
0.0242
Gnomad AMR
AF:
0.00490
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000384
Gnomad SAS
AF:
0.00868
Gnomad FIN
AF:
0.000753
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.00454
Gnomad OTH
AF:
0.0110
GnomAD2 exomes
AF:
0.00535
AC:
1279
AN:
239078
AF XY:
0.00525
show subpopulations
Gnomad AFR exome
AF:
0.0288
Gnomad AMR exome
AF:
0.00235
Gnomad ASJ exome
AF:
0.000875
Gnomad EAS exome
AF:
0.000228
Gnomad FIN exome
AF:
0.000287
Gnomad NFE exome
AF:
0.00423
Gnomad OTH exome
AF:
0.00435
GnomAD4 exome
AF:
0.00481
AC:
6965
AN:
1448250
Hom.:
41
Cov.:
32
AF XY:
0.00493
AC XY:
3553
AN XY:
720164
show subpopulations
African (AFR)
AF:
0.0288
AC:
939
AN:
32574
American (AMR)
AF:
0.00243
AC:
101
AN:
41642
Ashkenazi Jewish (ASJ)
AF:
0.000554
AC:
14
AN:
25266
East Asian (EAS)
AF:
0.0000505
AC:
2
AN:
39590
South Asian (SAS)
AF:
0.00899
AC:
759
AN:
84420
European-Finnish (FIN)
AF:
0.000665
AC:
35
AN:
52650
Middle Eastern (MID)
AF:
0.00613
AC:
35
AN:
5714
European-Non Finnish (NFE)
AF:
0.00432
AC:
4782
AN:
1106672
Other (OTH)
AF:
0.00499
AC:
298
AN:
59722
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
372
743
1115
1486
1858
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
198
396
594
792
990
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0108
AC:
1650
AN:
152388
Hom.:
12
Cov.:
33
AF XY:
0.0103
AC XY:
771
AN XY:
74526
show subpopulations
African (AFR)
AF:
0.0280
AC:
1166
AN:
41592
American (AMR)
AF:
0.00490
AC:
75
AN:
15312
Ashkenazi Jewish (ASJ)
AF:
0.000576
AC:
2
AN:
3470
East Asian (EAS)
AF:
0.000385
AC:
2
AN:
5192
South Asian (SAS)
AF:
0.00890
AC:
43
AN:
4832
European-Finnish (FIN)
AF:
0.000753
AC:
8
AN:
10630
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.00453
AC:
308
AN:
68040
Other (OTH)
AF:
0.0109
AC:
23
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
86
172
258
344
430
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00765
Hom.:
4
Bravo
AF:
0.0117
Asia WGS
AF:
0.00462
AC:
16
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Saldino-Mainzer syndrome Benign:2
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 12, 2018
Illumina Laboratory Services, Illumina
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Saldino-Mainzer syndrome;C4540439:Retinitis pigmentosa 80 Benign:1
Jul 20, 2021
Fulgent Genetics, Fulgent Genetics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.13
DANN
Benign
0.54
PhyloP100
-5.4
PromoterAI
-0.013
Neutral
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61745103; hg19: chr16-1569932; API