13-113822101-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000820.4(GAS6):c.1739C>T(p.Ser580Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,600,146 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., cov: 34)

Exomes 𝑓: 0.00072 ( 11 hom. )

Consequence

GAS6
NM_000820.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

Publications

1 publications found

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 was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.008088559).

BP6

Variant 13-113822101-G-A is Benign according to our data. Variant chr13-113822101-G-A is described in ClinVar as Benign. ClinVar VariationId is 781125.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 = 0.00659 (1004/152326) while in subpopulation AFR AF = 0.0221 (918/41574). AF 95% confidence interval is 0.0209. There are 10 homozygotes in GnomAd4. There are 491 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000820.4. 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
	GAS6	NM_000820.4	MANE Select	c.1739C>T	p.Ser580Leu	missense	Exon 14 of 15	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+6410G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAS6	ENST00000327773.7	TSL:1 MANE Select	c.1739C>T	p.Ser580Leu	missense	Exon 14 of 15	ENSP00000331831.6	Q14393-2
GAS6	ENST00000881729.1		c.2078C>T	p.Ser693Leu	missense	Exon 14 of 15	ENSP00000551788.1
GAS6	ENST00000881736.1		c.1931C>T	p.Ser644Leu	missense	Exon 14 of 15	ENSP00000551795.1

Frequencies

GnomAD3 genomes

AF:

0.00655

AC:

997

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00177

AC:

399

AN:

225570

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.0227

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000835

Gnomad FIN exome

AF:

0.000105

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000722

AC:

1045

AN:

1447820

Hom.:

Cov.:

AF XY:

0.000639

AC XY:

459

AN XY:

718850

show subpopulations

African (AFR)

AF:

0.0208

AC:

694

AN:

33414

American (AMR)

AF:

0.00156

AC:

AN:

42398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25688

East Asian (EAS)

AF:

0.000816

AC:

AN:

39192

South Asian (SAS)

AF:

0.0000360

AC:

AN:

83364

European-Finnish (FIN)

AF:

0.0000588

AC:

AN:

51056

Middle Eastern (MID)

AF:

0.00231

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.000121

AC:

134

AN:

1107140

Other (OTH)

AF:

0.00167

AC:

100

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00659

AC:

1004

AN:

152326

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

491

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.0221

AC:

918

AN:

41574

American (AMR)

AF:

0.00340

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5176

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68030

Other (OTH)

AF:

0.00569

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

148

197

246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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:

0.00388

Hom.:

Bravo

AF:

0.00761

ESP6500AA

AF:

0.0221

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00204

AC:

245

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0081

MetaSVM

Benign

-0.86

PhyloP100

1.2

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.21

Sift

Benign

0.23

Sift4G

Benign

0.39

Vest4

0.24

MVP

0.55

MPC

0.81

ClinPred

0.025

GERP RS

2.8

Varity_R

0.11

gMVP

0.73

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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