rs8191438

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-67583625-C-G
• chr11-67583625-C-T

Variant summary

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

The NM_000852.4(GSTP1):​c.-219C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0175 in 401,104 control chromosomes in the GnomAD database, including 642 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 0.027 (377 hom., cov: 33)
  • Exomes 𝑓: 0.012 (265 hom.)
• Consequence: GSTP1 NM_000852.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.-219C>G		upstream_gene_variant		ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.-219C>G		upstream_gene_variant		1	NM_000852.4	ENSP00000381607.3
GSTP1	ENST00000398603.6	c.-219C>G		upstream_gene_variant		3		ENSP00000381604.1
GSTP1	ENST00000494593.1	n.-197C>G		upstream_gene_variant		2
GSTP1	ENST00000646888.1	n.-219C>G		upstream_gene_variant				ENSP00000494477.1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4035 AN: 152072 Hom.: 375 Cov.: 33

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00326

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0119 AC: 2966 AN: 248924 Hom.: 265 Cov.: 0 AF XY: 0.0113 AC XY: 1435 AN XY: 127234

Gnomad4 AFR exome AF: 0.0179

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.00725

Gnomad4 EAS exome AF: 0.00874

Gnomad4 SAS exome AF: 0.000324

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00360

Gnomad4 OTH exome AF: 0.0227

GnomAD4 genome AF: 0.0265 AC: 4040 AN: 152180 Hom.: 377 Cov.: 33 AF XY: 0.0292 AC XY: 2171 AN XY: 74390

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00327

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.00120 Hom.: 1

Bravo AF: 0.0436

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs8191438; hg19: chr11-67351096;