13-113834544-C-T

Variant names:

• chr13-113834544-C-T
• rs8191974
• NM_000820.4:c.834+7G>A

Variant summary

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

The NM_000820.4(GAS6):​c.834+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,551,562 control chromosomes in the GnomAD database, including 71,109 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6371 hom., cov: 33)
  • Exomes 𝑓: 0.30 (64738 hom.)
• Consequence: GAS6 NM_000820.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001732
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185
• Publications: 39 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]

GAS6-AS1 (HGNC:39826): (GAS6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.319 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.834+7G>A		splice_region intron	N/A	NP_000811.1
	GAS6-AS1	NR_044995.2		n.171-140C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	ENST00000327773.7	TSL:1 MANE Select	c.834+7G>A		splice_region intron	N/A	ENSP00000331831.6
	GAS6-AS1	ENST00000458001.2	TSL:5	n.151-34C>T		intron	N/A
	GAS6	ENST00000610073.1	TSL:2	n.654+7G>A		splice_region intron	N/A

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43513 AN: 152012 Hom.: 6367 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.303

GnomAD2 exomes AF: 0.295 AC: 53028 AN: 179912 AF XY: 0.290

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.358

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.209

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.301 AC: 421618 AN: 1399432 Hom.: 64738 Cov.: 33 AF XY: 0.299 AC XY: 207294 AN XY: 692462

African (AFR) AF: 0.239 AC: 7487 AN: 31266

American (AMR) AF: 0.348 AC: 11695 AN: 33590

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 9752 AN: 24046

East Asian (EAS) AF: 0.205 AC: 7572 AN: 36988

South Asian (SAS) AF: 0.201 AC: 15714 AN: 78012

European-Finnish (FIN) AF: 0.297 AC: 14665 AN: 49348

Middle Eastern (MID) AF: 0.321 AC: 1583 AN: 4930

European-Non Finnish (NFE) AF: 0.310 AC: 335811 AN: 1083686

Other (OTH) AF: 0.301 AC: 17339 AN: 57566

GnomAD4 genome AF: 0.286 AC: 43544 AN: 152130 Hom.: 6371 Cov.: 33 AF XY: 0.285 AC XY: 21179 AN XY: 74366

African (AFR) AF: 0.236 AC: 9783 AN: 41516

American (AMR) AF: 0.326 AC: 4990 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3468

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5154

South Asian (SAS) AF: 0.205 AC: 989 AN: 4820

European-Finnish (FIN) AF: 0.309 AC: 3278 AN: 10600

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21155 AN: 67966

Other (OTH) AF: 0.301 AC: 635 AN: 2112

Alfa AF: 0.303 Hom.: 3327

Bravo AF: 0.288

Asia WGS AF: 0.189 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.94
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
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: rs8191974; hg19: chr13-114537517; COSMIC: COSV59848231; COSMIC: COSV59848231;