6-52978051-G-T

Variant names:

• chr6-52978051-G-T
• rs17614751
• NM_001512.4:c.*419C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001512.4(GSTA4):​c.*419C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000183 in 5,466 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: GSTA4 NM_001512.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	NM_001512.4	MANE Select	c.*419C>A		3_prime_UTR	Exon 7 of 7	NP_001503.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA4	ENST00000370963.9	TSL:1 MANE Select	c.*419C>A		3_prime_UTR	Exon 7 of 7	ENSP00000360002.4
	GSTA4	ENST00000477599.5	TSL:3	n.1029C>A		non_coding_transcript_exon	Exon 6 of 6
	GSTA4	ENST00000486559.5	TSL:2	n.1595C>A		non_coding_transcript_exon	Exon 5 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.000183 AC: 1 AN: 5466 Hom.: 0 Cov.: 0 AF XY: 0.000370 AC XY: 1 AN XY: 2700

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 76

American (AMR) AF: 0.00 AC: 0 AN: 76

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 112

East Asian (EAS) AF: 0.00 AC: 0 AN: 66

South Asian (SAS) AF: 0.00 AC: 0 AN: 294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 32

European-Non Finnish (NFE) AF: 0.000239 AC: 1 AN: 4192

Other (OTH) AF: 0.00 AC: 0 AN: 376

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.44
DANN	Benign	0.66
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17614751; hg19: chr6-52842849;