chr11-67586139-C-T

Position:

• chr11-67586139-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000852.4(GSTP1):​c.372C>T​(p.Pro124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,613,830 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: 𝑓 0.00014 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: GSTP1 NM_000852.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

Genes affected

GSTP1 (HGNC:4638): (glutathione S-transferase pi 1) Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into 4 main classes: alpha, mu, pi, and theta. This GST family member is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-2.56 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTP1	NM_000852.4	c.372C>T	p.Pro124=	synonymous_variant	6/7	ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.372C>T	p.Pro124=	synonymous_variant	6/7	1	NM_000852.4	P1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152036 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000562 AC: 14 AN: 249164 Hom.: 0 AF XY: 0.0000518 AC XY: 7 AN XY: 135200

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000841 AC: 123 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.0000770 AC XY: 56 AN XY: 727138

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000791

Gnomad4 OTH exome AF: 0.000116

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10 AN XY: 74366

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000148 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.39
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11553890; hg19: chr11-67353610;