NM_000820.4:c.1883-3C>T

Variant names:

• chr13-113821021-G-A
• rs141047065
• NM_000820.4:c.1883-3C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_000820.4(GAS6):​c.1883-3C>T variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,612,170 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0023 (11 hom.)
• Consequence: GAS6 NM_000820.4 splice_region, intron
• Scores: Splicing: ADA: 0.008116
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.35
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 13-113821021-G-A is Benign according to our data. Variant chr13-113821021-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 713017.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 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.1883-3C>T		splice_region intron	N/A	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.82+5330G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAS6	ENST00000327773.7	TSL:1 MANE Select	c.1883-3C>T		splice_region intron	N/A	ENSP00000331831.6	Q14393-2
	GAS6	ENST00000881731.1		c.1907C>T	p.Pro636Leu	missense	Exon 15 of 15	ENSP00000551790.1
	GAS6	ENST00000881729.1		c.2222-3C>T		splice_region intron	N/A	ENSP00000551788.1

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 253 AN: 152210 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00167 AC: 414 AN: 247580 AF XY: 0.00185

Gnomad AFR exome AF: 0.000563

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00110

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00190

Gnomad NFE exome AF: 0.00259

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00228 AC: 3332 AN: 1459842 Hom.: 11 Cov.: 31 AF XY: 0.00229 AC XY: 1662 AN XY: 726214

African (AFR) AF: 0.000359 AC: 12 AN: 33458

American (AMR) AF: 0.00143 AC: 64 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 28 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86216

European-Finnish (FIN) AF: 0.00144 AC: 75 AN: 52118

Middle Eastern (MID) AF: 0.00109 AC: 6 AN: 5510

European-Non Finnish (NFE) AF: 0.00273 AC: 3037 AN: 1111694

Other (OTH) AF: 0.00174 AC: 105 AN: 60328

GnomAD4 genome AF: 0.00166 AC: 253 AN: 152328 Hom.: 1 Cov.: 34 AF XY: 0.00146 AC XY: 109 AN XY: 74478

African (AFR) AF: 0.000505 AC: 21 AN: 41576

American (AMR) AF: 0.00137 AC: 21 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00278 AC: 189 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00210 Hom.: 0

Bravo AF: 0.00167

EpiCase AF: 0.00234

EpiControl AF: 0.00255

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.94
PhyloP100		8.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0081
dbscSNV1_RF	Benign	0.21
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: rs141047065; hg19: chr13-114523994;