ENST00000398603.6:c.-316C>A

Variant names:

• chr11-67583528-C-A
• rs36211088
• ENST00000398603.6:c.-316C>A

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.-316C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 312,834 control chromosomes in the GnomAD database, including 23,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11014 hom., cov: 32)
  • Exomes 𝑓: 0.38 (12264 hom.)
• Consequence: GSTP1 ENST00000398603.6 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 8 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=-0.86).
• BP6: Variant 11-67583528-C-A is Benign according to our data. Variant chr11-67583528-C-A is described in ClinVar as Benign. ClinVar VariationId is 1249154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000398603.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398603.6	TSL:3	c.-316C>A		upstream_gene	N/A	ENSP00000381604.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56611 AN: 151490 Hom.: 11013 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: 0.158

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.377 AC: 60725 AN: 161240 Hom.: 12264 AF XY: 0.379 AC XY: 31002 AN XY: 81870

African (AFR) AF: 0.395 AC: 1901 AN: 4818

American (AMR) AF: 0.265 AC: 1172 AN: 4418

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 1635 AN: 6150

East Asian (EAS) AF: 0.154 AC: 2262 AN: 14718

South Asian (SAS) AF: 0.304 AC: 489 AN: 1610

European-Finnish (FIN) AF: 0.349 AC: 4598 AN: 13184

Middle Eastern (MID) AF: 0.367 AC: 316 AN: 860

European-Non Finnish (NFE) AF: 0.423 AC: 44364 AN: 104786

Other (OTH) AF: 0.373 AC: 3988 AN: 10696

GnomAD4 genome AF: 0.374 AC: 56629 AN: 151594 Hom.: 11014 Cov.: 32 AF XY: 0.363 AC XY: 26854 AN XY: 74064

African (AFR) AF: 0.385 AC: 15936 AN: 41358

American (AMR) AF: 0.277 AC: 4227 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.157 AC: 813 AN: 5168

South Asian (SAS) AF: 0.294 AC: 1414 AN: 4806

European-Finnish (FIN) AF: 0.319 AC: 3346 AN: 10496

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

European-Non Finnish (NFE) AF: 0.425 AC: 28778 AN: 67722

Other (OTH) AF: 0.367 AC: 771 AN: 2102

Alfa AF: 0.390 Hom.: 1502

Bravo AF: 0.372

Asia WGS AF: 0.242 AC: 829 AN: 3422

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.3
DANN	Benign	0.36
PhyloP100		-1.1
PromoterAI		-0.032	Neutral

Splicing

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

Other links and lift over

dbSNP: rs36211088; hg19: chr11-67350999;