6-52984544-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001512.4(GSTA4):c.334T>C(p.Leu112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00621 in 1,613,222 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0043 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0064 (43 hom.)
• Consequence: GSTA4 NM_001512.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

Genes affected

GSTA4 (HGNC:4629): (glutathione S-transferase alpha 4) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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-tranferase belonging to the alpha class. The alpha class genes, which are located in a cluster on chromosome 6, are highly related and encode enzymes with glutathione peroxidase activity that function in the detoxification of lipid peroxidation products. Reactive electrophiles produced by oxidative metabolism have been linked to a number of degenerative diseases including Parkinson's disease, Alzheimer's disease, cataract formation, and atherosclerosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-52984544-A-G is Benign according to our data. Variant chr6-52984544-A-G is described in ClinVar as [Benign]. Clinvar id is 779335.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA4	NM_001512.4	c.334T>C	p.Leu112=	synonymous_variant	5/7	ENST00000370963.9
GSTA4	XM_005249035.5	c.334T>C	p.Leu112=	synonymous_variant	5/7
GSTA4	XM_011514534.4	c.223T>C	p.Leu75=	synonymous_variant	4/6
GSTA4	XM_011514535.4	c.223T>C	p.Leu75=	synonymous_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA4	ENST00000370963.9	c.334T>C	p.Leu112=	synonymous_variant	5/7	1	NM_001512.4	P1

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152216 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00758

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00408 AC: 1025 AN: 251426 Hom.: 8 AF XY: 0.00422 AC XY: 573 AN XY: 135888

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.00713

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00640 AC: 9352 AN: 1460888 Hom.: 43 Cov.: 31 AF XY: 0.00621 AC XY: 4515 AN XY: 726852

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.00382

Gnomad4 NFE exome AF: 0.00785

Gnomad4 OTH exome AF: 0.00419

GnomAD4 genome AF: 0.00434 AC: 661 AN: 152334 Hom.: 1 Cov.: 32 AF XY: 0.00396 AC XY: 295 AN XY: 74488

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.00756

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00597 Hom.: 3

Bravo AF: 0.00420

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00643

EpiControl AF: 0.00599

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 03, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	7.5
Dann	Benign	0.85

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

LitVar

Other links and lift over

dbSNP: rs45507994; hg19: chr6-52849342;