13-113846042-T-C

Position:

• chr13-113846042-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GAS6	NM_000820.4	c.343+485A>G		intron_variant		ENST00000327773.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAS6	ENST00000327773.7	c.343+485A>G		intron_variant		1	NM_000820.4	P1

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

Gnomad4 AFR AF: 0.841

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.508

Alfa AF: 0.414 Hom.: 21965

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

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: rs6602910; hg19: chr13-114549015;