rs8191973

Positions:

• chr13-113847856-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000820.4(GAS6):​c.280+170C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 683,022 control chromosomes in the GnomAD database, including 14,663 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 0.25 (7551 hom., cov: 32)
  • Exomes 𝑓: 0.14 (7112 hom.)
• Consequence: GAS6 NM_000820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS6	NM_000820.4	c.280+170C>G		intron_variant		ENST00000327773.7	NP_000811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.280+170C>G		intron_variant		1	NM_000820.4	ENSP00000331831.6
GAS6	ENST00000476291.1	n.376-18C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37990 AN: 151828 Hom.: 7512 Cov.: 32

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0959

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.223

GnomAD4 exome AF: 0.143 AC: 75823 AN: 531076 Hom.: 7112 Cov.: 6 AF XY: 0.143 AC XY: 41000 AN XY: 287616

Gnomad4 AFR exome AF: 0.560

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.0996

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.251 AC: 38094 AN: 151946 Hom.: 7551 Cov.: 32 AF XY: 0.248 AC XY: 18397 AN XY: 74260

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.0959

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.221

Alfa AF: 0.192 Hom.: 590

Bravo AF: 0.267

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.50

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: rs8191973; hg19: chr13-114550829;