rs8191439

Variant names:

• chr11-67583826-G-A
• rs8191439
• NM_000852.4:c.-18G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67583826-G-A
• chr11-67583826-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.307
• Publications: 11 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=-0.74).
• BP6: Variant 11-67583826-G-A is Benign according to our data. Variant chr11-67583826-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.-18G>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.-18G>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_000852.4	ENSP00000381607.3
GSTP1	ENST00000494593.1	n.5G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
GSTP1	ENST00000398603.6	c.-18G>A		5_prime_UTR_variant	Exon 1 of 6	3		ENSP00000381604.1
GSTP1	ENST00000646888.1	n.-18G>A		upstream_gene_variant				ENSP00000494477.1

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

GnomAD2 exomes AF: 0.0564 AC: 10302 AN: 182528 AF XY: 0.0421

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 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

African (AFR) AF: 0.0186 AC: 317 AN: 17044

American (AMR) AF: 0.308 AC: 11910 AN: 38652

Ashkenazi Jewish (ASJ) AF: 0.00919 AC: 186 AN: 20232

East Asian (EAS) AF: 0.0124 AC: 429 AN: 34502

South Asian (SAS) AF: 0.000707 AC: 46 AN: 65084

European-Finnish (FIN) AF: 0.000868 AC: 39 AN: 44940

Middle Eastern (MID) AF: 0.000679 AC: 2 AN: 2944

European-Non Finnish (NFE) AF: 0.00349 AC: 1172 AN: 335762

Other (OTH) AF: 0.0210 AC: 666 AN: 31702

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

African (AFR) AF: 0.0198 AC: 825 AN: 41580

American (AMR) AF: 0.181 AC: 2768 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.0261 AC: 135 AN: 5174

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00329 AC: 224 AN: 68014

Other (OTH) AF: 0.0246 AC: 52 AN: 2112

Alfa AF: 0.0143 Hom.: 174

Bravo AF: 0.0436

Asia WGS AF: 0.0230 AC: 81 AN: 3472

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	-0.74
CADD	Benign	8.5
DANN	Benign	0.74
PhyloP100		0.31
PromoterAI		0.11	Neutral
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

Other links and lift over

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