6-52985242-A-G

Variant names:

• chr6-52985242-A-G
• rs669674
• NM_001512.4:c.272+209T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001512.4(GSTA4):​c.272+209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,294 control chromosomes in the GnomAD database, including 65,586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.93 (65586 hom., cov: 32)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.63
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001512.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.272+209T>C		intron	N/A	NP_001503.1	O15217-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.272+209T>C		intron	N/A	ENSP00000360002.4	O15217-1
	GSTA4	ENST00000370959.1	TSL:5	c.272+209T>C		intron	N/A	ENSP00000359998.1	O15217-1
	GSTA4	ENST00000887782.1		c.272+209T>C		intron	N/A	ENSP00000557841.1

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141157 AN: 152176 Hom.: 65529 Cov.: 32

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.954

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.909

Gnomad OTH AF: 0.921

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.928 AC: 141272 AN: 152294 Hom.: 65586 Cov.: 32 AF XY: 0.929 AC XY: 69201 AN XY: 74472

African (AFR) AF: 0.938 AC: 38964 AN: 41554

American (AMR) AF: 0.940 AC: 14378 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 3312 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5185 AN: 5190

South Asian (SAS) AF: 0.985 AC: 4754 AN: 4826

European-Finnish (FIN) AF: 0.914 AC: 9697 AN: 10604

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61877 AN: 68034

Other (OTH) AF: 0.922 AC: 1949 AN: 2114

Alfa AF: 0.918 Hom.: 79812

Bravo AF: 0.929

Asia WGS AF: 0.986 AC: 3428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.19
DANN	Benign	0.37
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs669674;

hg19: chr6-52850040;