rs1803628

chr13-113827141-G-Achr13-113827141-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000820.4(GAS6):c.1332C>T(p.Cys444=) 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GAS6	NM_000820.4	c.1332C>T	p.Cys444=	synonymous_variant	12/15	ENST00000327773.7
GAS6-AS1	NR_044995.2	n.83-6351G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS6	ENST00000327773.7	c.1332C>T	p.Cys444=	synonymous_variant	12/15	1	NM_000820.4	P1
GAS6-AS1	ENST00000458001.2	n.63-6351G>A		intron_variant, non_coding_transcript_variant		5
GAS6	ENST00000480426.5	n.1487C>T		non_coding_transcript_exon_variant	4/7	2
GAS6	ENST00000610073.1	n.1152C>T		non_coding_transcript_exon_variant	6/9	2

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

GnomAD3 exomes AF: 0.161 AC: 40254 AN: 250312 Hom.: 4378 AF XY: 0.158 AC XY: 21460 AN XY: 135608

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 SAS exome AF: 0.290

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

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.258

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.0928

Gnomad4 NFE exome AF: 0.0930

Gnomad4 OTH exome AF: 0.127

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

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.0988

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.145

Alfa AF: 0.114 Hom.: 717

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

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