rs749174

Variant names:

• chr11-67585782-G-A
• rs749174
• NM_000852.4:c.337-322G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-67585782-G-A
• chr11-67585782-G-C
• chr11-67585782-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.337-322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,906 control chromosomes in the GnomAD database, including 6,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6808 hom., cov: 30)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.387
• Publications: 51 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=-0.64).
• BP6: Variant 11-67585782-G-A is Benign according to our data. Variant chr11-67585782-G-A is described in ClinVar as Benign. ClinVar VariationId is 1253210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	NM_000852.4	MANE Select	c.337-322G>A		intron	N/A	NP_000843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.337-322G>A		intron	N/A	ENSP00000381607.3
	GSTP1	ENST00000398603.6	TSL:3	c.336+541G>A		intron	N/A	ENSP00000381604.1
	GSTP1	ENST00000467591.1	TSL:2	n.448-322G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44379 AN: 151786 Hom.: 6800 Cov.: 30

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44413 AN: 151906 Hom.: 6808 Cov.: 30 AF XY: 0.284 AC XY: 21078 AN XY: 74236

African (AFR) AF: 0.261 AC: 10794 AN: 41406

American (AMR) AF: 0.223 AC: 3412 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3470

East Asian (EAS) AF: 0.153 AC: 784 AN: 5132

South Asian (SAS) AF: 0.241 AC: 1156 AN: 4800

European-Finnish (FIN) AF: 0.273 AC: 2896 AN: 10590

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23579 AN: 67932

Other (OTH) AF: 0.304 AC: 639 AN: 2104

Alfa AF: 0.319 Hom.: 11470

Bravo AF: 0.289

Asia WGS AF: 0.231 AC: 804 AN: 3478

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
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.7
DANN	Benign	0.91
PhyloP100		0.39
PromoterAI		-0.019	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs749174; hg19: chr11-67353253; COSMIC: COSV107508941; COSMIC: COSV107508941;