chr13-113822101-G-A

Position:

• chr13-113822101-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000820.4(GAS6):​c.1739C>T​(p.Ser580Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,600,146 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0066 (10 hom., cov: 34)
  • Exomes 𝑓: 0.00072 (11 hom.)
• Consequence: GAS6 NM_000820.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008088559).
• BP6: Variant 13-113822101-G-A is Benign according to our data. Variant chr13-113822101-G-A is described in ClinVar as [Benign]. Clinvar id is 781125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00659 (1004/152326) while in subpopulation AFR AF= 0.0221 (918/41574). AF 95% confidence interval is 0.0209. There are 10 homozygotes in gnomad4. There are 491 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAS6	NM_000820.4	c.1739C>T	p.Ser580Leu	missense_variant	14/15	ENST00000327773.7	NP_000811.1
GAS6-AS1	NR_044995.2	n.82+6410G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAS6	ENST00000327773.7	c.1739C>T	p.Ser580Leu	missense_variant	14/15	1	NM_000820.4	ENSP00000331831	P1
GAS6-AS1	ENST00000458001.2	n.62+6410G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 997 AN: 152208 Hom.: 10 Cov.: 34

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00575

GnomAD3 exomes AF: 0.00177 AC: 399 AN: 225570 Hom.: 1 AF XY: 0.00119 AC XY: 145 AN XY: 122240

Gnomad AFR exome AF: 0.0227

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000835

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000105

Gnomad NFE exome AF: 0.000138

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000722 AC: 1045 AN: 1447820 Hom.: 11 Cov.: 32 AF XY: 0.000639 AC XY: 459 AN XY: 718850

Gnomad4 AFR exome AF: 0.0208

Gnomad4 AMR exome AF: 0.00156

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000816

Gnomad4 SAS exome AF: 0.0000360

Gnomad4 FIN exome AF: 0.0000588

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.00167

GnomAD4 genome AF: 0.00659 AC: 1004 AN: 152326 Hom.: 10 Cov.: 34 AF XY: 0.00659 AC XY: 491 AN XY: 74476

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00347 Hom.: 2

Bravo AF: 0.00761

ESP6500AA AF: 0.0221 AC: 97

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00204 AC: 245

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	0.99
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.0081	T
MetaSVM	Benign	-0.86	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.21
Sift	Benign	0.23	T
Sift4G	Benign	0.39	T
Vest4		0.24
MVP		0.55
MPC		0.81
ClinPred		0.025	T
GERP RS		2.8
Varity_R		0.11
gMVP		0.73

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: rs79807310; hg19: chr13-114525074;