11-67583533-C-T

Variant names:

• chr11-67583533-C-T
• rs36211089
• ENST00000398603.6:c.-311C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000398603.6(GSTP1):​c.-311C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 320,478 control chromosomes in the GnomAD database, including 23,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11004 hom., cov: 32)
  • Exomes 𝑓: 0.38 (12971 hom.)
• Consequence: GSTP1 ENST00000398603.6 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.233
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-67583533-C-T is Benign according to our data. Variant chr11-67583533-C-T is described in ClinVar as Benign. ClinVar VariationId is 1240658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398603.6	c.-311C>T		upstream_gene_variant		3		ENSP00000381604.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56593 AN: 151514 Hom.: 11003 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.378 AC: 63830 AN: 168856 Hom.: 12971 AF XY: 0.380 AC XY: 32552 AN XY: 85748

African (AFR) AF: 0.393 AC: 1929 AN: 4912

American (AMR) AF: 0.262 AC: 1199 AN: 4570

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 1683 AN: 6368

East Asian (EAS) AF: 0.153 AC: 2342 AN: 15332

South Asian (SAS) AF: 0.331 AC: 635 AN: 1918

European-Finnish (FIN) AF: 0.351 AC: 4890 AN: 13938

Middle Eastern (MID) AF: 0.373 AC: 328 AN: 880

European-Non Finnish (NFE) AF: 0.425 AC: 46648 AN: 109732

Other (OTH) AF: 0.373 AC: 4176 AN: 11206

GnomAD4 genome AF: 0.373 AC: 56612 AN: 151622 Hom.: 11004 Cov.: 32 AF XY: 0.362 AC XY: 26853 AN XY: 74102

African (AFR) AF: 0.385 AC: 15930 AN: 41362

American (AMR) AF: 0.277 AC: 4223 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 901 AN: 3468

East Asian (EAS) AF: 0.157 AC: 811 AN: 5162

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4814

European-Finnish (FIN) AF: 0.319 AC: 3348 AN: 10494

Middle Eastern (MID) AF: 0.321 AC: 93 AN: 290

European-Non Finnish (NFE) AF: 0.425 AC: 28772 AN: 67762

Other (OTH) AF: 0.368 AC: 770 AN: 2094

Alfa AF: 0.409 Hom.: 15687

Bravo AF: 0.372

Asia WGS AF: 0.241 AC: 836 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.64
PhyloP100		-0.23
PromoterAI		-0.097	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs36211089; hg19: chr11-67351004; COSMIC: COSV66992373;