chr16-1587997-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014714.4(IFT140):c.838C>T(p.Arg280Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,613,818 control chromosomes in the GnomAD database, including 184 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R280Q) has been classified as Benign.

Frequency

Genomes: 𝑓 0.018 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

IFT140
NM_014714.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.67

Publications

7 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: G2P, Labcorp Genetics (formerly Invitae), 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

IFT140 links:

ENSG00000260989 (HGNC:):

ENSG00000260989 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003825456).

BP6

Variant 16-1587997-G-A is Benign according to our data. Variant chr16-1587997-G-A is described in ClinVar as Benign. ClinVar VariationId is 318202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT140	NM_014714.4	MANE Select	c.838C>T	p.Arg280Trp	missense	Exon 8 of 31	NP_055529.2
	LOC105371046	NR_135176.1		n.59+7412G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT140	ENST00000426508.7	TSL:5 MANE Select	c.838C>T	p.Arg280Trp	missense	Exon 8 of 31	ENSP00000406012.2	Q96RY7-1
IFT140	ENST00000889170.1		c.838C>T	p.Arg280Trp	missense	Exon 7 of 30	ENSP00000559229.1
IFT140	ENST00000962400.1		c.838C>T	p.Arg280Trp	missense	Exon 7 of 30	ENSP00000632459.1

Frequencies

GnomAD3 genomes

AF:

0.0183

AC:

2790

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0634

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.00479

AC:

1200

AN:

250660

AF XY:

0.00370

show subpopulations

Gnomad AFR exome

AF:

0.0639

Gnomad AMR exome

AF:

0.00325

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00194

AC:

2833

AN:

1461544

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1272

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.0641

AC:

2144

AN:

33456

American (AMR)

AF:

0.00371

AC:

166

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.000313

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00572

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000172

AC:

191

AN:

1111874

Other (OTH)

AF:

0.00445

AC:

269

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

134

267

401

534

668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0184

AC:

2798

AN:

152274

Hom.:

100

Cov.:

AF XY:

0.0177

AC XY:

1316

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0635

AC:

2637

AN:

41542

American (AMR)

AF:

0.00686

AC:

105

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68030

Other (OTH)

AF:

0.0123

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

133

266

398

531

664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0107

Hom.:

Bravo

AF:

0.0204

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0628

AC:

276

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00553

AC:

672

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Saldino-Mainzer syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

1.7

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.7

REVEL

Benign

0.077

Sift

Benign

0.034

Sift4G

Benign

0.13

Polyphen

0.99

Vest4

0.21

MVP

0.42

MPC

0.076

ClinPred

0.015

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.031

gMVP

0.49

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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