6-52978960-T-G

Variant names:

• chr6-52978960-T-G
• rs17614871
• NM_001512.4:c.547-368A>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.547-368A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,122 control chromosomes in the GnomAD database, including 228 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 0.046 (228 hom., cov: 31)
• Consequence: GSTA4 NM_001512.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 0 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 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.547-368A>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.547-368A>C		intron	N/A	ENSP00000360002.4	O15217-1
	GSTA4	ENST00000370959.1	TSL:5	c.547-368A>C		intron	N/A	ENSP00000359998.1	O15217-1
	GSTA4	ENST00000887782.1		c.547-368A>C		intron	N/A	ENSP00000557841.1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7065 AN: 152004 Hom.: 228 Cov.: 31

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0367

Gnomad FIN AF: 0.0665

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0675

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0464 AC: 7062 AN: 152122 Hom.: 228 Cov.: 31 AF XY: 0.0448 AC XY: 3333 AN XY: 74364

African (AFR) AF: 0.0117 AC: 486 AN: 41500

American (AMR) AF: 0.0468 AC: 715 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5164

South Asian (SAS) AF: 0.0365 AC: 176 AN: 4822

European-Finnish (FIN) AF: 0.0665 AC: 703 AN: 10572

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0675 AC: 4587 AN: 67980

Other (OTH) AF: 0.0459 AC: 97 AN: 2114

Alfa AF: 0.0210 Hom.: 192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.0
DANN	Benign	0.78
PhyloP100		0.35
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

Other links and lift over

dbSNP: rs17614871; hg19: chr6-52843758;