13-113834827-A-G

Variant names:

• chr13-113834827-A-G
• rs7323932
• NM_000820.4:c.713-155T>C

Variant summary

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

The NM_000820.4(GAS6):​c.713-155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 706,174 control chromosomes in the GnomAD database, including 59,524 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 0.45 (16300 hom., cov: 33)
  • Exomes 𝑓: 0.39 (43224 hom.)
• Consequence: GAS6 NM_000820.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAS6	NM_000820.4	c.713-155T>C		intron_variant	Intron 7 of 14	ENST00000327773.7	NP_000811.1
GAS6-AS1	NR_044995.2	n.251+63A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.713-155T>C		intron_variant	Intron 7 of 14	1	NM_000820.4	ENSP00000331831.6
GAS6-AS1	ENST00000458001.2	n.337+63A>G		intron_variant	Intron 3 of 4	5
GAS6	ENST00000610073.1	n.533-155T>C		intron_variant	Intron 1 of 8	2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68467 AN: 151972 Hom.: 16291 Cov.: 33

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.449

GnomAD4 exome AF: 0.387 AC: 214213 AN: 554084 Hom.: 43224 AF XY: 0.386 AC XY: 106718 AN XY: 276378

Gnomad4 AFR exome AF: 0.626

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.381

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.410

GnomAD4 genome AF: 0.451 AC: 68535 AN: 152090 Hom.: 16300 Cov.: 33 AF XY: 0.446 AC XY: 33180 AN XY: 74352

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.503

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.445

Alfa AF: 0.421 Hom.: 3097

Bravo AF: 0.458

Asia WGS AF: 0.308 AC: 1075 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7323932; hg19: chr13-114537800; COSMIC: COSV59853556; COSMIC: COSV59853556;