13-113847856-G-C

Variant names:

• chr13-113847856-G-C
• rs8191973
• NM_000820.4:c.280+170C>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.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
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000820.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	NM_000820.4	MANE Select	c.280+170C>G		intron	N/A	NP_000811.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	ENST00000327773.7	TSL:1 MANE Select	c.280+170C>G		intron	N/A	ENSP00000331831.6
	GAS6	ENST00000476291.1	TSL:2	n.376-18C>G		intron	N/A

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

African (AFR) AF: 0.560 AC: 7443 AN: 13288

American (AMR) AF: 0.202 AC: 4208 AN: 20876

Ashkenazi Jewish (ASJ) AF: 0.0996 AC: 1800 AN: 18066

East Asian (EAS) AF: 0.147 AC: 4658 AN: 31750

South Asian (SAS) AF: 0.185 AC: 9962 AN: 53860

European-Finnish (FIN) AF: 0.121 AC: 5496 AN: 45386

Middle Eastern (MID) AF: 0.197 AC: 608 AN: 3088

European-Non Finnish (NFE) AF: 0.118 AC: 37137 AN: 315888

Other (OTH) AF: 0.156 AC: 4511 AN: 28874

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

African (AFR) AF: 0.557 AC: 23063 AN: 41410

American (AMR) AF: 0.208 AC: 3164 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0959 AC: 333 AN: 3472

East Asian (EAS) AF: 0.144 AC: 741 AN: 5154

South Asian (SAS) AF: 0.182 AC: 873 AN: 4808

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10564

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7980 AN: 67984

Other (OTH) AF: 0.221 AC: 465 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.33
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: rs8191973; hg19: chr13-114550829;