Genetic Variant IFT172:c.5161-20G>A (chr2-27444541-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_015662.3(IFT172):c.5161-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,593,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

IFT172
NM_015662.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.01

Publications

0 publications found

Variant links:

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

IFT172 links:

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KRTCAP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 2-27444541-C-T is Benign according to our data. Variant chr2-27444541-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1529224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00067 (102/152286) while in subpopulation AFR AF = 0.00231 (96/41568). AF 95% confidence interval is 0.00194. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015662.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT172	NM_015662.3	MANE Select	c.5161-20G>A	intron	N/A	NP_056477.1	Q9UG01-1
IFT172	NM_001410739.1		c.5095-20G>A	intron	N/A	NP_001397668.1	A0A6Q8PGJ2
KRTCAP3	NM_001168364.2		c.*5+480C>T	intron	N/A	NP_001161836.1	Q53RY4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFT172	ENST00000260570.8	TSL:1 MANE Select	c.5161-20G>A	intron	N/A	ENSP00000260570.3	Q9UG01-1
IFT172	ENST00000509128.5	TSL:1	n.*606-20G>A	intron	N/A	ENSP00000427255.1	H0YAI8
IFT172	ENST00000945698.1		c.5272-20G>A	intron	N/A	ENSP00000615757.1

Frequencies

GnomAD3 genomes

AF:

0.000670

AC:

102

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000198

AC:

AN:

246954

AF XY:

0.000113

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.000264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000597

AC:

AN:

1441586

Hom.:

Cov.:

AF XY:

0.0000418

AC XY:

AN XY:

718300

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

33060

American (AMR)

AF:

0.000293

AC:

AN:

44426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25960

East Asian (EAS)

AF:

0.00

AC:

AN:

39614

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53066

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

9.13e-7

AC:

AN:

1094808

Other (OTH)

AF:

0.0000670

AC:

AN:

59732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000670

AC:

102

AN:

152286

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41568

American (AMR)

AF:

0.000262

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000214

Hom.:

Bravo

AF:

0.000722

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 (1)

Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71;C4310707:Bardet-Biedl syndrome 20 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.28

(source)

DANN

Benign

0.69

PhyloP100

-2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over