6-52796178-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145740.5(GSTA1):c.272+4C>T 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 0.00201 in 1,612,994 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (13 hom., cov: 28)
  • Exomes 𝑓: 0.0018 (46 hom.)
• Consequence: GSTA1 NM_145740.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.001522
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0150

Genes affected

GSTA1 (HGNC:4626): (glutathione S-transferase alpha 1) This gene encodes a member of a family of enzymes that function to add glutathione to target electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. This action is an important step in detoxification of these compounds. This subfamily of enzymes has a particular role in protecting cells from reactive oxygen species and the products of peroxidation. Polymorphisms in this gene influence the ability of individuals to metabolize different drugs. This gene is located in a cluster of similar genes and pseudogenes on chromosome 6. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 6-52796178-G-A is Benign according to our data. Variant chr6-52796178-G-A is described in ClinVar as [Benign]. Clinvar id is 718439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00369 (561/152052) while in subpopulation EAS AF= 0.0457 (236/5164). AF 95% confidence interval is 0.0409. There are 13 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA1	NM_145740.5	c.272+4C>T		splice_donor_region_variant, intron_variant		ENST00000334575.6
GSTA1	NM_001319059.2	c.-8+1408C>T		intron_variant
GSTA1	XM_005249034.5	c.272+4C>T		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA1	ENST00000334575.6	c.272+4C>T		splice_donor_region_variant, intron_variant		1	NM_145740.5	P1
GSTA1	ENST00000476213.1	n.326+4C>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		5
GSTA1	ENST00000493331.5	n.169+1408C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 151934 Hom.: 12 Cov.: 28

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0460

Gnomad SAS AF: 0.00209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00480

GnomAD3 exomes AF: 0.00450 AC: 1131 AN: 251210 Hom.: 18 AF XY: 0.00385 AC XY: 522 AN XY: 135760

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00951

Gnomad ASJ exome AF: 0.000694

Gnomad EAS exome AF: 0.0384

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00184 AC: 2684 AN: 1460942 Hom.: 46 Cov.: 31 AF XY: 0.00178 AC XY: 1292 AN XY: 726780

Gnomad4 AFR exome AF: 0.00260

Gnomad4 AMR exome AF: 0.0100

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.0461

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000702

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00369 AC: 561 AN: 152052 Hom.: 13 Cov.: 28 AF XY: 0.00423 AC XY: 314 AN XY: 74308

Gnomad4 AFR AF: 0.00299

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0457

Gnomad4 SAS AF: 0.00230

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00475

Alfa AF: 0.000514 Hom.: 0

Bravo AF: 0.00465

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	14
Dann	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0015
dbscSNV1_RF	Benign	0.064
SpliceAI score (max)		0.12		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: rs9367496; hg19: chr6-52660976;