11-67583826-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000852.4(GSTP1):c.-18G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 743,180 control chromosomes in the GnomAD database, including 2,537 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (375 hom., cov: 33)
  • Exomes 𝑓: 0.025 (2162 hom.)
• Consequence: GSTP1 NM_000852.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.307

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 11-67583826-G-A is Benign according to our data. Variant chr11-67583826-G-A is described in ClinVar as [Benign]. Clinvar id is 1246555.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
GSTP1	NM_000852.4	c.-18G>A		5_prime_UTR_variant	1/7	ENST00000398606.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTP1	ENST00000398606.10	c.-18G>A		5_prime_UTR_variant	1/7	1	NM_000852.4	P1
GSTP1	ENST00000398603.6	c.-18G>A		5_prime_UTR_variant	1/6	3
GSTP1	ENST00000494593.1	n.5G>A		non_coding_transcript_exon_variant	1/3	2
GSTP1	ENST00000646888.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4041 AN: 152208 Hom.: 373 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: 0.0260

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00329

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0564 AC: 10302 AN: 182528 Hom.: 1717 AF XY: 0.0421 AC XY: 4234 AN XY: 100680

Gnomad AFR exome AF: 0.0194

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.00838

Gnomad EAS exome AF: 0.0231

Gnomad SAS exome AF: 0.000633

Gnomad FIN exome AF: 0.000376

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.0367

GnomAD4 exome AF: 0.0250 AC: 14767 AN: 590862 Hom.: 2162 Cov.: 0 AF XY: 0.0199 AC XY: 6391 AN XY: 321004

Gnomad4 AFR exome AF: 0.0186

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.00919

Gnomad4 EAS exome AF: 0.0124

Gnomad4 SAS exome AF: 0.000707

Gnomad4 FIN exome AF: 0.000868

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.0210

GnomAD4 genome AF: 0.0266 AC: 4046 AN: 152318 Hom.: 375 Cov.: 33 AF XY: 0.0292 AC XY: 2174 AN XY: 74468

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0261

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00329

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.00720 Hom.: 39

Bravo AF: 0.0436

Asia WGS AF: 0.0230 AC: 81 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	8.5
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8191439; hg19: chr11-67351297; COSMIC: COSV66992564; COSMIC: COSV66992564;