11-67584303-C-T

Variant names:

• chr11-67584303-C-T
• rs2370143
• NM_000852.4:c.37+134C>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.37+134C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 748,850 control chromosomes in the GnomAD database, including 55,712 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8586 hom., cov: 32)
  • Exomes 𝑓: 0.38 (47126 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.944
• Publications: 8 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=-0.84).
• BP6: Variant 11-67584303-C-T is Benign according to our data. Variant chr11-67584303-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 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.37+134C>T		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+134C>T		intron	N/A	ENSP00000381607.3
	GSTP1	ENST00000494593.1	TSL:2	n.193C>T		non_coding_transcript_exon	Exon 2 of 3
	GSTP1	ENST00000398603.6	TSL:3	c.37+134C>T		intron	N/A	ENSP00000381604.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48268 AN: 151792 Hom.: 8592 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.328

GnomAD4 exome AF: 0.385 AC: 229669 AN: 596940 Hom.: 47126 Cov.: 8 AF XY: 0.382 AC XY: 120092 AN XY: 314494

African (AFR) AF: 0.195 AC: 2984 AN: 15284

American (AMR) AF: 0.232 AC: 4831 AN: 20826

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 3969 AN: 15240

East Asian (EAS) AF: 0.152 AC: 4914 AN: 32230

South Asian (SAS) AF: 0.313 AC: 16157 AN: 51626

European-Finnish (FIN) AF: 0.339 AC: 14462 AN: 42694

Middle Eastern (MID) AF: 0.332 AC: 977 AN: 2940

European-Non Finnish (NFE) AF: 0.442 AC: 170147 AN: 385208

Other (OTH) AF: 0.363 AC: 11228 AN: 30892

GnomAD4 genome AF: 0.318 AC: 48260 AN: 151910 Hom.: 8586 Cov.: 32 AF XY: 0.308 AC XY: 22894 AN XY: 74244

African (AFR) AF: 0.194 AC: 8024 AN: 41466

American (AMR) AF: 0.250 AC: 3826 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3464

East Asian (EAS) AF: 0.158 AC: 811 AN: 5126

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3384 AN: 10558

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28780 AN: 67868

Other (OTH) AF: 0.325 AC: 685 AN: 2108

Alfa AF: 0.238 Hom.: 610

Bravo AF: 0.307

Asia WGS AF: 0.238 AC: 827 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	-0.84
CADD	Benign	1.3
DANN	Benign	0.86
PhyloP100		-0.94
PromoterAI		-0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2370143; hg19: chr11-67351774; COSMIC: COSV66992693; COSMIC: COSV66992693;