rs17614751

Positions:

• chr6-52978051-G-A
• chr6-52978051-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001512.4(GSTA4):​c.*419C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 157,476 control chromosomes in the GnomAD database, including 245 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 (229 hom., cov: 32)
  • Exomes 𝑓: 0.068 (16 hom.)
• Consequence: GSTA4 NM_001512.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615

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]

GSTA4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTA4	NM_001512.4	c.*419C>T		3_prime_UTR_variant	7/7	ENST00000370963.9	NP_001503.1
GSTA4	XM_005249035.5	c.*419C>T		3_prime_UTR_variant	7/7		XP_005249092.1
GSTA4	XM_011514534.4	c.*419C>T		3_prime_UTR_variant	6/6		XP_011512836.1
GSTA4	XM_011514535.4	c.*419C>T		3_prime_UTR_variant	6/6		XP_011512837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTA4	ENST00000370963	c.*419C>T		3_prime_UTR_variant	7/7	1	NM_001512.4	ENSP00000360002.4
GSTA4	ENST00000477599.5	n.1029C>T		non_coding_transcript_exon_variant	6/6	3
GSTA4	ENST00000486559.5	n.1595C>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7063 AN: 151898 Hom.: 229 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0666

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0460

GnomAD4 exome AF: 0.0678 AC: 370 AN: 5460 Hom.: 16 Cov.: 0 AF XY: 0.0694 AC XY: 187 AN XY: 2696

Gnomad4 AFR exome AF: 0.0263

Gnomad4 AMR exome AF: 0.0789

Gnomad4 ASJ exome AF: 0.0893

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0476

Gnomad4 FIN exome AF: 0.0744

Gnomad4 NFE exome AF: 0.0709

Gnomad4 OTH exome AF: 0.0588

GnomAD4 genome AF: 0.0464 AC: 7060 AN: 152016 Hom.: 229 Cov.: 32 AF XY: 0.0449 AC XY: 3335 AN XY: 74308

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0373

Gnomad4 FIN AF: 0.0666

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0615 Hom.: 540

Bravo AF: 0.0443

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.64
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

Publications

LitVar

Other links and lift over

dbSNP: rs17614751; hg19: chr6-52842849;