6-52799253-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_145740.5(GSTA1):c.15C>T(p.Pro5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,698 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (21 hom.)
• Consequence: GSTA1 NM_145740.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.640

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 6-52799253-G-A is Benign according to our data. Variant chr6-52799253-G-A is described in ClinVar as [Benign]. Clinvar id is 726193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00147 (224/152274) while in subpopulation EAS AF= 0.0206 (107/5188). AF 95% confidence interval is 0.0175. There are 4 homozygotes in gnomad4. There are 112 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA1	NM_145740.5	c.15C>T	p.Pro5=	synonymous_variant	2/7	ENST00000334575.6
GSTA1	XM_005249034.5	c.15C>T	p.Pro5=	synonymous_variant	2/6
GSTA1	NM_001319059.2	c.-132C>T		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA1	ENST00000334575.6	c.15C>T	p.Pro5=	synonymous_variant	2/7	1	NM_145740.5	P1
GSTA1	ENST00000476213.1	n.121C>T		non_coding_transcript_exon_variant	2/4	5
GSTA1	ENST00000493331.5	n.45C>T		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152156 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00189 AC: 475 AN: 251150 Hom.: 4 AF XY: 0.00173 AC XY: 235 AN XY: 135712

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00218

Gnomad EAS exome AF: 0.0179

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.000475

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00109 AC: 1592 AN: 1461424 Hom.: 21 Cov.: 31 AF XY: 0.00114 AC XY: 830 AN XY: 727042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00172

Gnomad4 EAS exome AF: 0.0270

Gnomad4 SAS exome AF: 0.00122

Gnomad4 FIN exome AF: 0.000917

Gnomad4 NFE exome AF: 0.000196

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152274 Hom.: 4 Cov.: 32 AF XY: 0.00150 AC XY: 112 AN XY: 74468

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00106 Hom.: 0

Bravo AF: 0.00195

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000237

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.2
Dann	Benign	0.45

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: rs75442307; hg19: chr6-52664051; COSMIC: COSV58015438;