11-67583625-C-T

Variant names:

• chr11-67583625-C-T
• rs8191438
• NM_000852.4:c.-219C>T

Variant summary

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

The NM_000852.4(GSTP1):​c.-219C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 401,046 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: GSTP1 NM_000852.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 6 publications found

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

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=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000852.4. 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
	GSTP1	NM_000852.4	MANE Select	c.-219C>T		upstream_gene	N/A	NP_000843.1	P09211

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.-219C>T		upstream_gene	N/A	ENSP00000381607.3	P09211
	GSTP1	ENST00000495996.2	TSL:2	c.-219C>T		upstream_gene	N/A	ENSP00000484686.2
	GSTP1	ENST00000906565.1		c.-219C>T		upstream_gene	N/A	ENSP00000576624.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 4 AN: 248960 Hom.: 0 Cov.: 0 AF XY: 0.0000157 AC XY: 2 AN XY: 127258

African (AFR) AF: 0.00 AC: 0 AN: 6468

American (AMR) AF: 0.00 AC: 0 AN: 6832

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8696

East Asian (EAS) AF: 0.00 AC: 0 AN: 21398

South Asian (SAS) AF: 0.00 AC: 0 AN: 6170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1256

European-Non Finnish (NFE) AF: 0.0000250 AC: 4 AN: 160158

Other (OTH) AF: 0.00 AC: 0 AN: 16032

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152086 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74284

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.97
PhyloP100		-0.86
PromoterAI		-0.023	Neutral

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: rs8191438; hg19: chr11-67351096;