11-67586373-C-T

Variant names:

• chr11-67586373-C-T
• rs1871042
• NM_000852.4:c.445-16C>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.445-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,599,400 control chromosomes in the GnomAD database, including 88,654 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7016 hom., cov: 32)
  • Exomes 𝑓: 0.33 (81638 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830
• Publications: 48 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=-0.83).
• BP6: Variant 11-67586373-C-T is Benign according to our data. Variant chr11-67586373-C-T is described in ClinVar as Benign. ClinVar VariationId is 1288111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	NM_000852.4	MANE Select	c.445-16C>T		intron	N/A	NP_000843.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.445-16C>T		intron	N/A	ENSP00000381607.3
	GSTP1	ENST00000495996.2	TSL:2	c.505-16C>T		intron	N/A	ENSP00000484686.2
	GSTP1	ENST00000906565.1		c.442-16C>T		intron	N/A	ENSP00000576624.1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45160 AN: 152018 Hom.: 7007 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.306

GnomAD2 exomes AF: 0.281 AC: 67604 AN: 240862 AF XY: 0.286

Gnomad AFR exome AF: 0.279

Gnomad AMR exome AF: 0.189

Gnomad ASJ exome AF: 0.211

Gnomad EAS exome AF: 0.151

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.309

GnomAD4 exome AF: 0.331 AC: 478795 AN: 1447264 Hom.: 81638 Cov.: 32 AF XY: 0.329 AC XY: 236412 AN XY: 718614

African (AFR) AF: 0.276 AC: 9150 AN: 33138

American (AMR) AF: 0.192 AC: 8360 AN: 43476

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 5504 AN: 25378

East Asian (EAS) AF: 0.147 AC: 5796 AN: 39512

South Asian (SAS) AF: 0.261 AC: 22220 AN: 85046

European-Finnish (FIN) AF: 0.285 AC: 15094 AN: 53026

Middle Eastern (MID) AF: 0.311 AC: 1770 AN: 5696

European-Non Finnish (NFE) AF: 0.356 AC: 391979 AN: 1102274

Other (OTH) AF: 0.317 AC: 18922 AN: 59718

GnomAD4 genome AF: 0.297 AC: 45189 AN: 152136 Hom.: 7016 Cov.: 32 AF XY: 0.289 AC XY: 21492 AN XY: 74358

African (AFR) AF: 0.276 AC: 11474 AN: 41518

American (AMR) AF: 0.227 AC: 3478 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3470

East Asian (EAS) AF: 0.153 AC: 790 AN: 5166

South Asian (SAS) AF: 0.242 AC: 1167 AN: 4828

European-Finnish (FIN) AF: 0.274 AC: 2897 AN: 10586

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23602 AN: 67962

Other (OTH) AF: 0.303 AC: 641 AN: 2114

Alfa AF: 0.322 Hom.: 11242

Bravo AF: 0.294

Asia WGS AF: 0.229 AC: 799 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	-0.83
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.083
PromoterAI		-0.0038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1871042; hg19: chr11-67353844; COSMIC: COSV66992473; COSMIC: COSV66992473;