chr11-67586499-T-C

Variant names:

• chr11-67586499-T-C
• rs4891
• NM_000852.4:c.555T>C

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.555T>C​(p.Ser185Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,613,388 control chromosomes in the GnomAD database, including 104,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11609 hom., cov: 33)
  • Exomes 𝑓: 0.35 (92586 hom.)
• Consequence: GSTP1 NM_000852.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.935
• Publications: 62 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=-0.94).
• BP6: Variant 11-67586499-T-C is Benign according to our data. Variant chr11-67586499-T-C is described in ClinVar as Benign. ClinVar VariationId is 1281843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.935 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.555T>C	p.Ser185Ser	synonymous_variant	Exon 7 of 7	ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.555T>C	p.Ser185Ser	synonymous_variant	Exon 7 of 7	1	NM_000852.4	ENSP00000381607.3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57622 AN: 152076 Hom.: 11594 Cov.: 33

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.371

GnomAD2 exomes AF: 0.346 AC: 86223 AN: 249046 AF XY: 0.334

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.176

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.345

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.350 AC: 511957 AN: 1461194 Hom.: 92586 Cov.: 38 AF XY: 0.346 AC XY: 251352 AN XY: 726954

African (AFR) AF: 0.497 AC: 16626 AN: 33468

American (AMR) AF: 0.517 AC: 23110 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5902 AN: 26132

East Asian (EAS) AF: 0.160 AC: 6358 AN: 39696

South Asian (SAS) AF: 0.263 AC: 22713 AN: 86228

European-Finnish (FIN) AF: 0.285 AC: 15240 AN: 53402

Middle Eastern (MID) AF: 0.317 AC: 1827 AN: 5764

European-Non Finnish (NFE) AF: 0.359 AC: 399486 AN: 1111466

Other (OTH) AF: 0.343 AC: 20695 AN: 60370

GnomAD4 genome AF: 0.379 AC: 57676 AN: 152194 Hom.: 11609 Cov.: 33 AF XY: 0.371 AC XY: 27600 AN XY: 74396

African (AFR) AF: 0.488 AC: 20275 AN: 41534

American (AMR) AF: 0.430 AC: 6579 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3472

East Asian (EAS) AF: 0.177 AC: 917 AN: 5174

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4826

European-Finnish (FIN) AF: 0.273 AC: 2898 AN: 10598

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23885 AN: 67980

Other (OTH) AF: 0.368 AC: 777 AN: 2112

Alfa AF: 0.360 Hom.: 19192

Bravo AF: 0.401

Asia WGS AF: 0.260 AC: 906 AN: 3478

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 09, 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	-0.94
CADD	Benign	0.62
DANN	Benign	0.26
PhyloP100		-0.94
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4891; hg19: chr11-67353970; COSMIC: COSV66992478; COSMIC: COSV66992478;