11-67584690-C-T

Variant names:

• chr11-67584690-C-T
• rs8191448
• NM_000852.4:c.150C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000852.4(GSTP1):​c.150C>T​(p.Tyr50Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00904 in 1,613,170 control chromosomes in the GnomAD database, including 1,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (595 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (573 hom.)
• Consequence: GSTP1 NM_000852.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-67584690-C-T is Benign according to our data. Variant chr11-67584690-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

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.150C>T	p.Tyr50Tyr	synonymous	Exon 4 of 7	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.150C>T	p.Tyr50Tyr	synonymous	Exon 4 of 7	ENSP00000381607.3	P09211
	GSTP1	ENST00000914376.1		c.43C>T	p.Arg15Trp	missense	Exon 3 of 6	ENSP00000584435.1
	GSTP1	ENST00000495996.2	TSL:2	c.150C>T	p.Tyr50Tyr	synonymous	Exon 4 of 7	ENSP00000484686.2

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7415 AN: 152148 Hom.: 596 Cov.: 33

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.0392

GnomAD2 exomes AF: 0.0119 AC: 2962 AN: 249016 AF XY: 0.00841

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.00760

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000443

Gnomad OTH exome AF: 0.00447

GnomAD4 exome AF: 0.00490 AC: 7165 AN: 1460904 Hom.: 573 Cov.: 32 AF XY: 0.00409 AC XY: 2969 AN XY: 726790

African (AFR) AF: 0.176 AC: 5885 AN: 33426

American (AMR) AF: 0.00874 AC: 391 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5766

European-Non Finnish (NFE) AF: 0.000261 AC: 290 AN: 1111332

Other (OTH) AF: 0.00933 AC: 563 AN: 60364

GnomAD4 genome AF: 0.0488 AC: 7424 AN: 152266 Hom.: 595 Cov.: 33 AF XY: 0.0461 AC XY: 3434 AN XY: 74448

African (AFR) AF: 0.169 AC: 7016 AN: 41532

American (AMR) AF: 0.0188 AC: 287 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68016

Other (OTH) AF: 0.0388 AC: 82 AN: 2112

Alfa AF: 0.0206 Hom.: 121

Bravo AF: 0.0547

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000533

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.74
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs8191448; hg19: chr11-67352161;