13-113846042-T-C

Variant names:

• chr13-113846042-T-C
• rs6602910
• NM_000820.4:c.343+485A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000820.4(GAS6):​c.343+485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,154 control chromosomes in the GnomAD database, including 24,461 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 0.53 (24461 hom., cov: 34)
• Consequence: GAS6 NM_000820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4	c.343+485A>G		intron_variant	Intron 4 of 14	ENST00000327773.7	NP_000811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.343+485A>G		intron_variant	Intron 4 of 14	1	NM_000820.4	ENSP00000331831.6

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80675 AN: 152036 Hom.: 24401 Cov.: 34

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.505

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80800 AN: 152154 Hom.: 24461 Cov.: 34 AF XY: 0.531 AC XY: 39525 AN XY: 74384

African (AFR) AF: 0.841 AC: 34927 AN: 41540

American (AMR) AF: 0.484 AC: 7403 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1586 AN: 3468

East Asian (EAS) AF: 0.459 AC: 2367 AN: 5160

South Asian (SAS) AF: 0.578 AC: 2791 AN: 4826

European-Finnish (FIN) AF: 0.387 AC: 4098 AN: 10582

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26030 AN: 67980

Other (OTH) AF: 0.508 AC: 1073 AN: 2114

Alfa AF: 0.426 Hom.: 38643

Bravo AF: 0.544

Asia WGS AF: 0.579 AC: 2014 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.029
DANN	Benign	0.37
PhyloP100		-1.9
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: rs6602910; hg19: chr13-114549015;