Genetic Variant GAS6:c.713-155T>C (chr13-113834827-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000820.4(GAS6):c.713-155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 706,174 control chromosomes in the GnomAD database, including 59,524 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 16300 hom., cov: 33)

Exomes 𝑓: 0.39 ( 43224 hom. )

Consequence

GAS6
NM_000820.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

7 publications found

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:39826): (GAS6 antisense RNA 1)

GAS6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

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.713-155T>C		intron	N/A	NP_000811.1	Q14393-2
	GAS6-AS1	NR_044995.2		n.251+63A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GAS6	ENST00000327773.7	TSL:1 MANE Select	c.713-155T>C	intron	N/A	ENSP00000331831.6	Q14393-2
GAS6	ENST00000881729.1		c.1052-155T>C	intron	N/A	ENSP00000551788.1
GAS6	ENST00000881736.1		c.905-155T>C	intron	N/A	ENSP00000551795.1

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68467

AN:

151972

Hom.:

16291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.503

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.449

GnomAD4 exome

AF:

0.387

AC:

214213

AN:

554084

Hom.:

43224

AF XY:

0.386

AC XY:

106718

AN XY:

276378

show subpopulations

African (AFR)

AF:

0.626

AC:

8297

AN:

13248

American (AMR)

AF:

0.366

AC:

4405

AN:

12030

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

5856

AN:

11376

East Asian (EAS)

AF:

0.248

AC:

6412

AN:

25880

South Asian (SAS)

AF:

0.381

AC:

5084

AN:

13336

European-Finnish (FIN)

AF:

0.362

AC:

8388

AN:

23190

Middle Eastern (MID)

AF:

0.491

AC:

955

AN:

1946

European-Non Finnish (NFE)

AF:

0.384

AC:

163919

AN:

426500

Other (OTH)

AF:

0.410

AC:

10897

AN:

26578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

6243

12487

18730

24974

31217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4382

8764

13146

17528

21910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.451

AC:

68535

AN:

152090

Hom.:

16300

Cov.:

AF XY:

0.446

AC XY:

33180

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.614

AC:

25482

AN:

41476

American (AMR)

AF:

0.412

AC:

6307

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.503

AC:

1748

AN:

3472

East Asian (EAS)

AF:

0.257

AC:

1332

AN:

5176

South Asian (SAS)

AF:

0.379

AC:

1827

AN:

4816

European-Finnish (FIN)

AF:

0.361

AC:

3820

AN:

10576

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.391

AC:

26580

AN:

67968

Other (OTH)

AF:

0.445

AC:

939

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1953

3906

5860

7813

9766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.414

Hom.:

21148

Bravo

AF:

0.458

Asia WGS

AF:

0.308

AC:

1075

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.51

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over