chr13-113823530-C-T

Position:

chr13-113823530-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000820.4(GAS6):c.1498G>A(p.Gly500Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,612,172 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.011 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 42 hom. )

Consequence

GAS6
NM_000820.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

GAS6 (HGNC:4168): (growth arrest specific 6) This gene encodes a gamma-carboxyglutamic acid (Gla)-containing protein thought to be involved in the stimulation of cell proliferation. This gene is frequently overexpressed in many cancers and has been implicated as an adverse prognostic marker. Elevated protein levels are additionally associated with a variety of disease states, including venous thromboembolic disease, systemic lupus erythematosus, chronic renal failure, and preeclampsia. [provided by RefSeq, Aug 2014]

GAS6 links:

GAS6-AS1 (HGNC:39826): (GAS6 antisense RNA 1)

GAS6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037489831).

BP6

Variant 13-113823530-C-T is Benign according to our data. Variant chr13-113823530-C-T is described in ClinVar as [Benign]. Clinvar id is 791330.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 = 0.0111 (1685/152312) while in subpopulation AFR AF= 0.0391 (1626/41570). AF 95% confidence interval is 0.0375. There are 25 homozygotes in gnomad4. There are 741 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS6	NM_000820.4 linkuse as main transcript	c.1498G>A	p.Gly500Arg	missense_variant	13/15	ENST00000327773.7
GAS6-AS1	NR_044995.2 linkuse as main transcript	n.82+7839C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS6	ENST00000327773.7 linkuse as main transcript	c.1498G>A	p.Gly500Arg	missense_variant	13/15	1	NM_000820.4	P1	Q14393-2
GAS6-AS1	ENST00000458001.2 linkuse as main transcript	n.62+7839C>T		intron_variant, non_coding_transcript_variant		5
GAS6	ENST00000480426.5 linkuse as main transcript	n.1653G>A		non_coding_transcript_exon_variant	5/7	2
GAS6	ENST00000610073.1 linkuse as main transcript	n.1318G>A		non_coding_transcript_exon_variant	7/9	2

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1677

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0390

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00279

AC:

697

AN:

249740

Hom.:

AF XY:

0.00191

AC XY:

258

AN XY:

135294

show subpopulations

Gnomad AFR exome

AF:

0.0388

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000987

GnomAD4 exome

AF:

0.00115

AC:

1677

AN:

1459860

Hom.:

Cov.:

AF XY:

0.000935

AC XY:

679

AN XY:

726152

show subpopulations

Gnomad4 AFR exome

AF:

0.0425

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.0111

AC:

1685

AN:

152312

Hom.:

Cov.:

AF XY:

0.00995

AC XY:

741

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0391

Gnomad4 AMR

AF:

0.00300

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.0124

ESP6500AA

AF:

0.0350

AC:

154

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00340

AC:

413

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.85

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.7

REVEL

Benign

0.21

Sift

Benign

0.13

Sift4G

Benign

0.18

Vest4

0.29

MVP

0.57

MPC

0.90

ClinPred

0.024

GERP RS

4.0

Varity_R

0.034

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over