Variant chr1-109713540-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_000851.4(GSTM5):c.234C>G(p.Arg78Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00597 in 1,613,106 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 75 hom. )

Consequence

GSTM5
NM_000851.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) 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. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

GSTM5 links:

GSTM5 (HGNC:):

GSTM5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-109713540-C-G is Benign according to our data. Variant chr1-109713540-C-G is described in ClinVar as [Benign]. Clinvar id is 784446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00585 (885/151252) while in subpopulation SAS AF= 0.019 (91/4796). AF 95% confidence interval is 0.0158. There are 6 homozygotes in gnomad4. There are 441 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM5	NM_000851.4 linkuse as main transcript	c.234C>G	p.Arg78Arg	synonymous_variant	4/8	ENST00000256593.8	NP_000842.2	P46439Q5T8R2
GSTM5	XM_005270784.5 linkuse as main transcript	c.234C>G	p.Arg78Arg	synonymous_variant	5/9		XP_005270841.1	P46439Q5T8R2
GSTM5	XM_005270785.5 linkuse as main transcript	c.-53-121C>G		intron_variant			XP_005270842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8 linkuse as main transcript	c.234C>G	p.Arg78Arg	synonymous_variant	4/8	1	NM_000851.4	ENSP00000256593.3		P46439

Frequencies

GnomAD3 genomes

AF:

0.00584

AC:

882

AN:

151134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00315

Gnomad AMI

AF:

0.00774

Gnomad AMR

AF:

0.00514

Gnomad ASJ

AF:

0.00809

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0185

Gnomad FIN

AF:

0.00805

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00650

Gnomad OTH

AF:

0.00962

GnomAD3 exomes

AF:

0.00755

AC:

1900

AN:

251492

Hom.:

AF XY:

0.00845

AC XY:

1149

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00962

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.00979

Gnomad NFE exome

AF:

0.00592

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.00598

AC:

8742

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00668

AC XY:

4861

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00257

Gnomad4 AMR exome

AF:

0.00362

Gnomad4 ASJ exome

AF:

0.00934

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.0230

Gnomad4 FIN exome

AF:

0.00944

Gnomad4 NFE exome

AF:

0.00469

Gnomad4 OTH exome

AF:

0.00695

GnomAD4 genome

AF:

0.00585

AC:

885

AN:

151252

Hom.:

Cov.:

AF XY:

0.00597

AC XY:

441

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.00316

Gnomad4 AMR

AF:

0.00513

Gnomad4 ASJ

AF:

0.00809

Gnomad4 EAS

AF:

0.000969

Gnomad4 SAS

AF:

0.0190

Gnomad4 FIN

AF:

0.00805

Gnomad4 NFE

AF:

0.00650

Gnomad4 OTH

AF:

0.00951

Alfa

AF:

0.00724

Hom.:

Bravo

AF:

0.00530

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.00818

EpiControl

AF:

0.00735

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.28

Position offset: -1

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