chr13-113827141-G-A

Variant names:

• chr13-113827141-G-A
• rs1803628
• NM_000820.4:c.1332C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000820.4(GAS6):​c.1332C>T​(p.Cys444Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,612,610 control chromosomes in the GnomAD database, including 15,772 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 0.16 (2505 hom., cov: 31)
  • Exomes 𝑓: 0.12 (13267 hom.)
• Consequence: GAS6 NM_000820.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 17 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.049 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4	c.1332C>T	p.Cys444Cys	synonymous_variant	Exon 12 of 15	ENST00000327773.7	NP_000811.1
GAS6-AS1	NR_044995.2	n.83-6351G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.1332C>T	p.Cys444Cys	synonymous_variant	Exon 12 of 15	1	NM_000820.4	ENSP00000331831.6
GAS6	ENST00000480426.5	n.1487C>T		non_coding_transcript_exon_variant	Exon 4 of 7	2
GAS6	ENST00000610073.1	n.1152C>T		non_coding_transcript_exon_variant	Exon 6 of 9	2
GAS6-AS1	ENST00000458001.2	n.63-6351G>A		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24797 AN: 151758 Hom.: 2493 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.161 AC: 40254 AN: 250312 AF XY: 0.158

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.0638

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.0925

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.118 AC: 172208 AN: 1460734 Hom.: 13267 Cov.: 32 AF XY: 0.121 AC XY: 88216 AN XY: 726662

African (AFR) AF: 0.284 AC: 9488 AN: 33438

American (AMR) AF: 0.258 AC: 11512 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0643 AC: 1680 AN: 26124

East Asian (EAS) AF: 0.210 AC: 8339 AN: 39680

South Asian (SAS) AF: 0.286 AC: 24640 AN: 86184

European-Finnish (FIN) AF: 0.0928 AC: 4912 AN: 52914

Middle Eastern (MID) AF: 0.0931 AC: 536 AN: 5760

European-Non Finnish (NFE) AF: 0.0930 AC: 103410 AN: 1111604

Other (OTH) AF: 0.127 AC: 7691 AN: 60362

GnomAD4 genome AF: 0.163 AC: 24830 AN: 151876 Hom.: 2505 Cov.: 31 AF XY: 0.166 AC XY: 12311 AN XY: 74224

African (AFR) AF: 0.276 AC: 11415 AN: 41360

American (AMR) AF: 0.186 AC: 2842 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0646 AC: 224 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1054 AN: 5128

South Asian (SAS) AF: 0.301 AC: 1444 AN: 4794

European-Finnish (FIN) AF: 0.0988 AC: 1045 AN: 10576

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0947 AC: 6435 AN: 67972

Other (OTH) AF: 0.145 AC: 305 AN: 2106

Alfa AF: 0.122 Hom.: 1054

Bravo AF: 0.174

Asia WGS AF: 0.314 AC: 1092 AN: 3478

EpiCase AF: 0.0862

EpiControl AF: 0.0865

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.1
DANN	Benign	0.76
PhyloP100		0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1803628; hg19: chr13-114530114; COSMIC: COSV59848469; COSMIC: COSV59848469;