Genetic Variant GAS6:c.712+26G>A (chr13-113835487-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000820.4(GAS6):c.712+26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,609,196 control chromosomes in the GnomAD database, including 18,665 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1465 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17200 hom. )

Consequence

GAS6
NM_000820.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4 link	c.712+26G>A		intron_variant	Intron 7 of 14	ENST00000327773.7	NP_000811.1
GAS6-AS1	NR_044995.2 link	n.251+723C>T		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GAS6	ENST00000327773.7 link	c.712+26G>A	intron_variant	Intron 7 of 14	1	NM_000820.4	ENSP00000331831.6
GAS6-AS1	ENST00000458001.2 link	n.337+723C>T	intron_variant	Intron 3 of 4	5
GAS6	ENST00000610073.1 link	n.532+26G>A	intron_variant	Intron 1 of 8	2

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20079

AN:

152022

Hom.:

1465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0962

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0414

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.124

AC:

30612

AN:

246722

AF XY:

0.124

show subpopulations

Gnomad AFR exome

AF:

0.0893

Gnomad AMR exome

AF:

0.0835

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.00126

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.146

AC:

213262

AN:

1457058

Hom.:

17200

Cov.:

AF XY:

0.144

AC XY:

104405

AN XY:

724422

show subpopulations

African (AFR)

AF:

0.0927

AC:

3098

AN:

33404

American (AMR)

AF:

0.0895

AC:

3986

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

7323

AN:

26050

East Asian (EAS)

AF:

0.000656

AC:

AN:

39642

South Asian (SAS)

AF:

0.0465

AC:

4003

AN:

86046

European-Finnish (FIN)

AF:

0.149

AC:

7750

AN:

51898

Middle Eastern (MID)

AF:

0.137

AC:

780

AN:

5692

European-Non Finnish (NFE)

AF:

0.160

AC:

177394

AN:

1109592

Other (OTH)

AF:

0.148

AC:

8902

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

8907

17814

26721

35628

44535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6066

12132

18198

24264

30330

<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:

0.132

AC:

20077

AN:

152138

Hom.:

1465

Cov.:

AF XY:

0.129

AC XY:

9608

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0960

AC:

3985

AN:

41504

American (AMR)

AF:

0.124

AC:

1899

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

970

AN:

3472

East Asian (EAS)

AF:

0.00213

AC:

AN:

5170

South Asian (SAS)

AF:

0.0412

AC:

199

AN:

4830

European-Finnish (FIN)

AF:

0.145

AC:

1542

AN:

10598

Middle Eastern (MID)

AF:

0.170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10968

AN:

67958

Other (OTH)

AF:

0.138

AC:

290

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

883

1766

2648

3531

4414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.144

Hom.:

657

Bravo

AF:

0.129

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.024

(source)

DANN

Benign

0.91

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over