11-67584203-G-A

Variant names:

• chr11-67584203-G-A
• rs8191445
• NM_000852.4:c.37+34G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 72 AR gene

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.37+34G>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.37+34G>A		intron	N/A	ENSP00000381607.3
	GSTP1	ENST00000494593.1	TSL:2	n.93G>A		non_coding_transcript_exon	Exon 2 of 3
	GSTP1	ENST00000398603.6	TSL:3	c.37+34G>A		intron	N/A	ENSP00000381604.1

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

GnomAD2 exomes AF: 0.0278 AC: 6716 AN: 241730 AF XY: 0.0278

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 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

African (AFR) AF: 0.00499 AC: 163 AN: 32694

American (AMR) AF: 0.00688 AC: 305 AN: 44354

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 647 AN: 25678

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39376

South Asian (SAS) AF: 0.00983 AC: 835 AN: 84968

European-Finnish (FIN) AF: 0.0696 AC: 3687 AN: 52986

Middle Eastern (MID) AF: 0.00548 AC: 31 AN: 5662

European-Non Finnish (NFE) AF: 0.0370 AC: 39282 AN: 1060872

Other (OTH) AF: 0.0278 AC: 1625 AN: 58370

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

African (AFR) AF: 0.00576 AC: 239 AN: 41522

American (AMR) AF: 0.0104 AC: 159 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3468

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5136

South Asian (SAS) AF: 0.0101 AC: 49 AN: 4828

European-Finnish (FIN) AF: 0.0711 AC: 754 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0379 AC: 2573 AN: 67920

Other (OTH) AF: 0.0199 AC: 42 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.76
PhyloP100		-0.28
PromoterAI		-0.033	Neutral
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

Other links and lift over

dbSNP: rs8191445; hg19: chr11-67351674;