rs8191445

Positions:

• chr11-67584203-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000852.4(GSTP1):​c.37+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 1,557,038 control chromosomes in the GnomAD database, including 1,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (72 hom., cov: 32)
  • Exomes 𝑓: 0.033 (955 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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]

GSTP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0258 (3925/152078) while in subpopulation NFE AF= 0.0379 (2573/67920). AF 95% confidence interval is 0.0367. There are 72 homozygotes in gnomad4. There are 1945 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 72 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.37+34G>A		intron_variant		ENST00000398606.10	NP_000843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTP1	ENST00000398606.10	c.37+34G>A		intron_variant		1	NM_000852.4	ENSP00000381607.3

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3927 AN: 151964 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.00577

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0104

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0202

GnomAD3 exomes AF: 0.0278 AC: 6716 AN: 241730 Hom.: 163 AF XY: 0.0278 AC XY: 3677 AN XY: 132156

Gnomad AFR exome AF: 0.00580

Gnomad AMR exome AF: 0.00656

Gnomad ASJ exome AF: 0.0234

Gnomad EAS exome AF: 0.000226

Gnomad SAS exome AF: 0.0101

Gnomad FIN exome AF: 0.0685

Gnomad NFE exome AF: 0.0394

Gnomad OTH exome AF: 0.0286

GnomAD4 exome AF: 0.0332 AC: 46581 AN: 1404960 Hom.: 955 Cov.: 26 AF XY: 0.0327 AC XY: 22968 AN XY: 701734

Gnomad4 AFR exome AF: 0.00499

Gnomad4 AMR exome AF: 0.00688

Gnomad4 ASJ exome AF: 0.0252

Gnomad4 EAS exome AF: 0.000152

Gnomad4 SAS exome AF: 0.00983

Gnomad4 FIN exome AF: 0.0696

Gnomad4 NFE exome AF: 0.0370

Gnomad4 OTH exome AF: 0.0278

GnomAD4 genome AF: 0.0258 AC: 3925 AN: 152078 Hom.: 72 Cov.: 32 AF XY: 0.0262 AC XY: 1945 AN XY: 74362

Gnomad4 AFR AF: 0.00576

Gnomad4 AMR AF: 0.0104

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0379

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0313 Hom.: 15

Bravo AF: 0.0201

Asia WGS AF: 0.00492 AC: 17 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6

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: rs8191445; hg19: chr11-67351674;