chr13-113821993-C-T

Position:

chr13-113821993-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.1847G>A(p.Arg616Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,549,070 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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 0.0070 ( 10 hom., cov: 34)

Exomes 𝑓: 0.00068 ( 12 hom. )

Consequence

GAS6
NM_000820.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.26

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=0.0032764375).

BP6

Variant 13-113821993-C-T is Benign according to our data. Variant chr13-113821993-C-T is described in ClinVar as [Benign]. Clinvar id is 787414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-113821993-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00704 (1072/152324) while in subpopulation AFR AF= 0.0246 (1023/41570). AF 95% confidence interval is 0.0234. There are 10 homozygotes in gnomad4. There are 518 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAS6	NM_000820.4 linkuse as main transcript	c.1847G>A	p.Arg616Gln	missense_variant	14/15	ENST00000327773.7
GAS6-AS1	NR_044995.2 linkuse as main transcript	n.82+6302C>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.1847G>A	p.Arg616Gln	missense_variant	14/15	1	NM_000820.4	P1	Q14393-2
GAS6-AS1	ENST00000458001.2 linkuse as main transcript	n.62+6302C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00704

AC:

1071

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00235

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:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00170

AC:

257

AN:

151448

Hom.:

AF XY:

0.00108

AC XY:

AN XY:

81408

show subpopulations

Gnomad AFR exome

AF:

0.0269

Gnomad AMR exome

AF:

0.000760

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000860

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000677

Gnomad OTH exome

AF:

0.000911

GnomAD4 exome

AF:

0.000683

AC:

954

AN:

1396746

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

400

AN XY:

689358

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.000970

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000549

Gnomad4 SAS exome

AF:

0.0000756

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000222

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00704

AC:

1072

AN:

152324

Hom.:

Cov.:

AF XY:

0.00695

AC XY:

518

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0246

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00135

Hom.:

Bravo

AF:

0.00741

ESP6500AA

AF:

0.0243

AC:

103

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.00155

AC:

175

Asia WGS

AF:

0.00202

AC:

AN:

3478

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.9

DANN

Benign

0.85

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

1.0

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.12

MVP

0.51

MPC

0.27

ClinPred

0.0046

GERP RS

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.027

gMVP

0.24

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