rs11807

chr1-109718120-T-C

Variant summary

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

The NM_000851.4(GSTM5):c.*694T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 152,366 control chromosomes in the GnomAD database, including 2,421 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 0.17 (2417 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: GSTM5 NM_000851.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. 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-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM5	NM_000851.4	c.*694T>C		3_prime_UTR_variant	8/8	ENST00000256593.8
GSTM5	XM_005270784.5	c.*694T>C		3_prime_UTR_variant	9/9
GSTM5	XM_005270785.5	c.*694T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM5	ENST00000256593.8	c.*694T>C		3_prime_UTR_variant	8/8	1	NM_000851.4	P3
GSTM5	ENST00000369813.5	n.4229T>C		non_coding_transcript_exon_variant	5/5	2
GSTM5	ENST00000429410.2	n.82+5772T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26280 AN: 152032 Hom.: 2411 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.139 AC: 30 AN: 216 Hom.: 4 Cov.: 0 AF XY: 0.156 AC XY: 25 AN XY: 160

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.173 AC: 26306 AN: 152150 Hom.: 2417 Cov.: 32 AF XY: 0.173 AC XY: 12894 AN XY: 74384

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.160

Alfa AF: 0.190 Hom.: 5989

Bravo AF: 0.168

Asia WGS AF: 0.169 AC: 589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.74
Dann	Benign	0.65

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: rs11807; hg19: chr1-110260742;