Genetic Variant NM_015714.4:c.*65T>G (chr1-209676061-T-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_015714.4(G0S2):c.*65T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 1,320,082 control chromosomes in the GnomAD database, including 627,454 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 0.97 ( 71765 hom., cov: 33)

Exomes 𝑓: 0.97 ( 555689 hom. )

Consequence

G0S2
NM_015714.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.75

Publications

7 publications found

Variant links:

Genes affected

G0S2 (HGNC:30229): (G0/G1 switch 2) Involved in extrinsic apoptotic signaling pathway and positive regulation of extrinsic apoptotic signaling pathway. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

G0S2 links:

HSD11B1-AS1 (HGNC:54053): (HSD11B1 antisense RNA 1)

HSD11B1-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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
G0S2	NM_015714.4	MANE Select	c.*65T>G	3_prime_UTR	Exon 2 of 2	NP_056529.1	P27469
HSD11B1-AS1	NR_134509.1		n.97-13000A>C	intron	N/A
HSD11B1-AS1	NR_134510.1		n.67-13000A>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
G0S2	ENST00000367029.5	TSL:1 MANE Select	c.*65T>G	3_prime_UTR	Exon 2 of 2	ENSP00000355996.4	P27469
G0S2	ENST00000891678.1		c.*65T>G	3_prime_UTR	Exon 2 of 2	ENSP00000561737.1
G0S2	ENST00000891679.1		c.*65T>G	3_prime_UTR	Exon 2 of 2	ENSP00000561738.1

Frequencies

GnomAD3 genomes

AF:

0.969

AC:

147467

AN:

152146

Hom.:

71706

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.893

Gnomad ASJ

AF:

0.994

Gnomad EAS

AF:

0.740

Gnomad SAS

AF:

0.953

Gnomad FIN

AF:

0.989

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.985

Gnomad OTH

AF:

0.972

GnomAD4 exome

AF:

0.974

AC:

1137789

AN:

1167818

Hom.:

555689

Cov.:

AF XY:

0.974

AC XY:

559706

AN XY:

574596

show subpopulations

African (AFR)

AF:

0.996

AC:

26248

AN:

26350

American (AMR)

AF:

0.854

AC:

20220

AN:

23686

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

17996

AN:

18094

East Asian (EAS)

AF:

0.739

AC:

26836

AN:

36316

South Asian (SAS)

AF:

0.959

AC:

60244

AN:

62812

European-Finnish (FIN)

AF:

0.988

AC:

47088

AN:

47668

Middle Eastern (MID)

AF:

0.973

AC:

3403

AN:

3498

European-Non Finnish (NFE)

AF:

0.987

AC:

887856

AN:

899896

Other (OTH)

AF:

0.968

AC:

47898

AN:

49498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1438

2877

4315

5754

7192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17398

34796

52194

69592

86990

<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:

0.969

AC:

147584

AN:

152264

Hom.:

71765

Cov.:

AF XY:

0.966

AC XY:

71908

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.994

AC:

41330

AN:

41580

American (AMR)

AF:

0.893

AC:

13648

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.994

AC:

3452

AN:

3472

East Asian (EAS)

AF:

0.741

AC:

3811

AN:

5140

South Asian (SAS)

AF:

0.953

AC:

4599

AN:

4826

European-Finnish (FIN)

AF:

0.989

AC:

10499

AN:

10614

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.985

AC:

66986

AN:

68020

Other (OTH)

AF:

0.972

AC:

2057

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

213

426

639

852

1065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.979

Hom.:

67460

Bravo

AF:

0.962

Asia WGS

AF:

0.878

AC:

3053

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

(source)

DANN

Benign

0.34

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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