chr13-113856449-A-G

Variant names:

• chr13-113856449-A-G
• rs7997328
• NM_000820.4:c.255+7126T>C

Variant summary

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

The NM_000820.4(GAS6):​c.255+7126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,004 control chromosomes in the GnomAD database, including 17,161 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 0.44 (17161 hom., cov: 32)
• Consequence: GAS6 NM_000820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873
• Publications: 3 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4	c.255+7126T>C		intron_variant	Intron 2 of 14	ENST00000327773.7	NP_000811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.255+7126T>C		intron_variant	Intron 2 of 14	1	NM_000820.4	ENSP00000331831.6
GAS6	ENST00000476291.1	n.350+7126T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66159 AN: 151886 Hom.: 17126 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.436 AC: 66255 AN: 152004 Hom.: 17161 Cov.: 32 AF XY: 0.440 AC XY: 32690 AN XY: 74292

African (AFR) AF: 0.724 AC: 29983 AN: 41430

American (AMR) AF: 0.404 AC: 6172 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2419 AN: 5158

South Asian (SAS) AF: 0.566 AC: 2721 AN: 4804

European-Finnish (FIN) AF: 0.312 AC: 3302 AN: 10582

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19451 AN: 67976

Other (OTH) AF: 0.421 AC: 885 AN: 2102

Alfa AF: 0.341 Hom.: 6178

Bravo AF: 0.448

Asia WGS AF: 0.568 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.33
PhyloP100		-0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs7997328; hg19: chr13-114559422;