rs74663534

Variant names:

• chr13-113822049-G-A
• rs74663534
• NM_000820.4:c.1791C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000820.4(GAS6):​c.1791C>T​(p.Ser597Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000698 in 1,582,260 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (1 hom., cov: 34)
  • Exomes 𝑓: 0.00070 (11 hom.)
• Consequence: GAS6 NM_000820.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 13-113822049-G-A is Benign according to our data. Variant chr13-113822049-G-A is described in ClinVar as Benign. ClinVar VariationId is 731365.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.12 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000697 (997/1429932) while in subpopulation EAS AF = 0.0191 (734/38460). AF 95% confidence interval is 0.0179. There are 11 homozygotes in GnomAdExome4. There are 512 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 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.1791C>T	p.Ser597Ser	synonymous	Exon 14 of 15	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+6358G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	ENST00000327773.7	TSL:1 MANE Select	c.1791C>T	p.Ser597Ser	synonymous	Exon 14 of 15	ENSP00000331831.6	Q14393-2
	GAS6	ENST00000881729.1		c.2130C>T	p.Ser710Ser	synonymous	Exon 14 of 15	ENSP00000551788.1
	GAS6	ENST00000881736.1		c.1983C>T	p.Ser661Ser	synonymous	Exon 14 of 15	ENSP00000551795.1

Frequencies

GnomAD3 genomes AF: 0.000703 AC: 107 AN: 152210 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00139 AC: 274 AN: 196738 AF XY: 0.00138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0121

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000198

GnomAD4 exome AF: 0.000697 AC: 997 AN: 1429932 Hom.: 11 Cov.: 32 AF XY: 0.000723 AC XY: 512 AN XY: 708318

African (AFR) AF: 0.00 AC: 0 AN: 33130

American (AMR) AF: 0.00277 AC: 109 AN: 39350

Ashkenazi Jewish (ASJ) AF: 0.0000392 AC: 1 AN: 25490

East Asian (EAS) AF: 0.0191 AC: 734 AN: 38460

South Asian (SAS) AF: 0.000441 AC: 36 AN: 81682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49352

Middle Eastern (MID) AF: 0.000386 AC: 2 AN: 5186

European-Non Finnish (NFE) AF: 0.0000811 AC: 89 AN: 1098026

Other (OTH) AF: 0.000439 AC: 26 AN: 59256

GnomAD4 genome AF: 0.000702 AC: 107 AN: 152328 Hom.: 1 Cov.: 34 AF XY: 0.000819 AC XY: 61 AN XY: 74486

African (AFR) AF: 0.0000240 AC: 1 AN: 41580

American (AMR) AF: 0.00144 AC: 22 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0141 AC: 73 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68026

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000183 Hom.: 0

Bravo AF: 0.000858

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.72
DANN	Benign	0.85
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs74663534; hg19: chr13-114525022; COSMIC: COSV59847026;