Variant chr1-109669374-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000848.4(GSTM2):c.259+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,614,222 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 45 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 50 hom. )

Consequence

GSTM2
NM_000848.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.0006587

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71

Variant links:

Genes affected

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. [provided by RefSeq, Jul 2008]

GSTM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-109669374-G-A is Benign according to our data. Variant chr1-109669374-G-A is described in ClinVar as [Benign]. Clinvar id is 775572.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0139 (2112/152336) while in subpopulation AFR AF= 0.0484 (2012/41568). AF 95% confidence interval is 0.0466. There are 45 homozygotes in gnomad4. There are 1004 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GSTM2	NM_000848.4 linkuse as main transcript	c.259+3G>A	splice_donor_region_variant, intron_variant	ENST00000241337.9
GSTM2	NM_001142368.2 linkuse as main transcript	c.259+3G>A	splice_donor_region_variant, intron_variant
GSTM2	XR_007059236.1 linkuse as main transcript	n.318+3G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant
GSTM2	XR_007059237.1 linkuse as main transcript	n.318+3G>A	splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM2	ENST00000241337.9 linkuse as main transcript	c.259+3G>A		splice_donor_region_variant, intron_variant		1	NM_000848.4	P1	P28161-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2109

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00340

AC:

856

AN:

251494

Hom.:

AF XY:

0.00258

AC XY:

350

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0481

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00141

AC:

2061

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

861

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0515

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00318

GnomAD4 genome

AF:

0.0139

AC:

2112

AN:

152336

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0484

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00770

Hom.:

Bravo

AF:

0.0158

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00066

dbscSNV1_RF

Benign

0.028

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over