Variant 13-113834544-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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 links:

GAS6-AS1 (HGNC:):

GAS6-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS6	NM_000820.4 linkuse as main transcript	c.834+7G>A		splice_region_variant, intron_variant		ENST00000327773.7	NP_000811.1	Q14393-2
GAS6-AS1	NR_044995.2 linkuse as main transcript	n.171-140C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
GAS6	ENST00000327773.7 linkuse as main transcript	c.834+7G>A	splice_region_variant, intron_variant	1	NM_000820.4	ENSP00000331831.6	Q14393-2
GAS6-AS1	ENST00000458001.2 linkuse as main transcript	n.151-34C>T	intron_variant	5
GAS6	ENST00000610073.1 linkuse as main transcript	n.654+7G>A	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43513

AN:

152012

Hom.:

6367

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.295

AC:

53028

AN:

179912

Hom.:

8110

AF XY:

0.290

AC XY:

28495

AN XY:

98184

show subpopulations

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 SAS exome

AF:

0.201

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.:

AF XY:

0.299

AC XY:

207294

AN XY:

692462

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.406

Gnomad4 EAS exome

AF:

0.205

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.286

AC:

43544

AN:

152130

Hom.:

6371

Cov.:

AF XY:

0.285

AC XY:

21179

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.326

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.310

Hom.:

2259

Bravo

AF:

0.288

Asia WGS

AF:

0.189

AC:

659

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.8

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over