chr13-113822036-C-T

Variant names:

• chr13-113822036-C-T
• rs144262744
• NM_000820.4:c.1804G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000820.4(GAS6):​c.1804G>A​(p.Ala602Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,574,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: GAS6 NM_000820.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.877
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042018294).
• BP6: Variant 13-113822036-C-T is Benign according to our data. Variant chr13-113822036-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3518921.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1804G>A	p.Ala602Thr	missense	Exon 14 of 15	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+6345C>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.1804G>A	p.Ala602Thr	missense	Exon 14 of 15	ENSP00000331831.6	Q14393-2
	GAS6	ENST00000881729.1		c.2143G>A	p.Ala715Thr	missense	Exon 14 of 15	ENSP00000551788.1
	GAS6	ENST00000881736.1		c.1996G>A	p.Ala666Thr	missense	Exon 14 of 15	ENSP00000551795.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152218 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000151 AC: 28 AN: 185056 AF XY: 0.000170

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.000114

Gnomad EAS exome AF: 0.000143

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000241

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000212 AC: 302 AN: 1422340 Hom.: 0 Cov.: 32 AF XY: 0.000190 AC XY: 134 AN XY: 703980

African (AFR) AF: 0.00 AC: 0 AN: 32976

American (AMR) AF: 0.000130 AC: 5 AN: 38428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25404

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38050

South Asian (SAS) AF: 0.0000493 AC: 4 AN: 81072

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48368

Middle Eastern (MID) AF: 0.000199 AC: 1 AN: 5032

European-Non Finnish (NFE) AF: 0.000260 AC: 284 AN: 1094026

Other (OTH) AF: 0.000119 AC: 7 AN: 58984

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152336 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41586

American (AMR) AF: 0.00 AC: 0 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000247 Hom.: 0

Bravo AF: 0.000125

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000234 AC: 2

ExAC AF: 0.000143 AC: 17

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.91
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.88
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.12
Sift	Benign	0.39	T
Sift4G	Benign	0.58	T
Vest4		0.097
MVP		0.37
MPC		0.23
ClinPred		0.0062	T
GERP RS		-3.9
Varity_R		0.030
gMVP		0.46
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs144262744; hg19: chr13-114525009;