13-113822006-C-T

Variant names:

• chr13-113822006-C-T
• rs73583241
• NM_000820.4:c.1834G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000820.4(GAS6):​c.1834G>A​(p.Glu612Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,556,086 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (45 hom., cov: 34)
  • Exomes 𝑓: 0.0013 (36 hom.)
• Consequence: GAS6 NM_000820.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0770
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029712021).
• BP6: Variant 13-113822006-C-T is Benign according to our data. Variant chr13-113822006-C-T is described in ClinVar as Benign. ClinVar VariationId is 786243.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 = 0.0136 (2073/152344) while in subpopulation AFR AF = 0.0461 (1915/41574). AF 95% confidence interval is 0.0443. There are 45 homozygotes in GnomAd4. There are 959 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 45 gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	NM_000820.4	MANE Select	c.1834G>A	p.Glu612Lys	missense	Exon 14 of 15	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+6315C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	ENST00000327773.7	TSL:1 MANE Select	c.1834G>A	p.Glu612Lys	missense	Exon 14 of 15	ENSP00000331831.6	Q14393-2
	GAS6	ENST00000881729.1		c.2173G>A	p.Glu725Lys	missense	Exon 14 of 15	ENSP00000551788.1
	GAS6	ENST00000881736.1		c.2026G>A	p.Glu676Lys	missense	Exon 14 of 15	ENSP00000551795.1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2072 AN: 152226 Hom.: 45 Cov.: 34

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00330 AC: 527 AN: 159730 AF XY: 0.00253

Gnomad AFR exome AF: 0.0481

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00132 AC: 1848 AN: 1403742 Hom.: 36 Cov.: 32 AF XY: 0.00111 AC XY: 768 AN XY: 693320

African (AFR) AF: 0.0460 AC: 1491 AN: 32384

American (AMR) AF: 0.00320 AC: 117 AN: 36582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25206

East Asian (EAS) AF: 0.0000271 AC: 1 AN: 36896

South Asian (SAS) AF: 0.000113 AC: 9 AN: 79766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45122

Middle Eastern (MID) AF: 0.00123 AC: 6 AN: 4880

European-Non Finnish (NFE) AF: 0.0000387 AC: 42 AN: 1084610

Other (OTH) AF: 0.00312 AC: 182 AN: 58296

GnomAD4 genome AF: 0.0136 AC: 2073 AN: 152344 Hom.: 45 Cov.: 34 AF XY: 0.0129 AC XY: 959 AN XY: 74492

African (AFR) AF: 0.0461 AC: 1915 AN: 41574

American (AMR) AF: 0.00771 AC: 118 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68034

Other (OTH) AF: 0.0128 AC: 27 AN: 2112

Alfa AF: 0.00112 Hom.: 5

Bravo AF: 0.0162

ESP6500AA AF: 0.0460 AC: 197

ESP6500EA AF: 0.000353 AC: 3

ExAC AF: 0.00301 AC: 348

Asia WGS AF: 0.00144 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.4
DANN	Benign	0.93
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.077
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.17
Sift	Benign	0.36	T
Sift4G	Benign	0.24	T
Vest4		0.14
MVP		0.82
MPC		0.27
ClinPred		0.0046	T
GERP RS		1.2
Varity_R		0.037
gMVP		0.69
Mutation Taster		=92/8	polymorphism

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: rs73583241; hg19: chr13-114524979;