dbSNP rs8191973: GAS6:c.280+170C>G (chr13-113847856-G-C) – 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.280+170C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 683,022 control chromosomes in the GnomAD database, including 14,663 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 0.25 ( 7551 hom., cov: 32)

Exomes 𝑓: 0.14 ( 7112 hom. )

Consequence

GAS6
NM_000820.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334

Publications

8 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:

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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4 link	c.280+170C>G		intron_variant	Intron 3 of 14	ENST00000327773.7	NP_000811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7 link	c.280+170C>G		intron_variant	Intron 3 of 14	1	NM_000820.4	ENSP00000331831.6
GAS6	ENST00000476291.1 link	n.376-18C>G		intron_variant	Intron 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37990

AN:

151828

Hom.:

7512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.0959

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.123

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.223

GnomAD4 exome

AF:

0.143

AC:

75823

AN:

531076

Hom.:

7112

Cov.:

AF XY:

0.143

AC XY:

41000

AN XY:

287616

show subpopulations

African (AFR)

AF:

0.560

AC:

7443

AN:

13288

American (AMR)

AF:

0.202

AC:

4208

AN:

20876

Ashkenazi Jewish (ASJ)

AF:

0.0996

AC:

1800

AN:

18066

East Asian (EAS)

AF:

0.147

AC:

4658

AN:

31750

South Asian (SAS)

AF:

0.185

AC:

9962

AN:

53860

European-Finnish (FIN)

AF:

0.121

AC:

5496

AN:

45386

Middle Eastern (MID)

AF:

0.197

AC:

608

AN:

3088

European-Non Finnish (NFE)

AF:

0.118

AC:

37137

AN:

315888

Other (OTH)

AF:

0.156

AC:

4511

AN:

28874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

3099

6198

9298

12397

15496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<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:

0.251

AC:

38094

AN:

151946

Hom.:

7551

Cov.:

AF XY:

0.248

AC XY:

18397

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.557

AC:

23063

AN:

41410

American (AMR)

AF:

0.208

AC:

3164

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.0959

AC:

333

AN:

3472

East Asian (EAS)

AF:

0.144

AC:

741

AN:

5154

South Asian (SAS)

AF:

0.182

AC:

873

AN:

4808

European-Finnish (FIN)

AF:

0.123

AC:

1300

AN:

10564

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.117

AC:

7980

AN:

67984

Other (OTH)

AF:

0.221

AC:

465

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1156

2313

3469

4626

5782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.192

Hom.:

590

Bravo

AF:

0.267

Asia WGS

AF:

0.186

AC:

649

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.7

(source)

DANN

Benign

0.50

PhyloP100

-0.33

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