11-67584060-G-A

Position:

• chr11-67584060-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000852.4(GSTP1):​c.2-74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,260,962 control chromosomes in the GnomAD database, including 118,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11120 hom., cov: 33)
  • Exomes 𝑓: 0.43 (107020 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.605

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-67584060-G-A is Benign according to our data. Variant chr11-67584060-G-A is described in ClinVar as [Benign]. Clinvar id is 1282703.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTP1	NM_000852.4	c.2-74G>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.2-74G>A		intron_variant		1	NM_000852.4	ENSP00000381607.3
GSTP1	ENST00000398603.6	c.2-74G>A		intron_variant		3		ENSP00000381604.1
GSTP1	ENST00000494593.1	n.24-74G>A		intron_variant		2
GSTP1	ENST00000646888.1	n.2-74G>A		intron_variant				ENSP00000494477.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 56896 AN: 151196 Hom.: 11119 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.374

GnomAD4 exome AF: 0.429 AC: 476548 AN: 1109656 Hom.: 107020 Cov.: 15 AF XY: 0.425 AC XY: 239361 AN XY: 563226

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.268

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.404

GnomAD4 genome AF: 0.376 AC: 56918 AN: 151306 Hom.: 11120 Cov.: 33 AF XY: 0.365 AC XY: 27004 AN XY: 73944

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.371

Alfa AF: 0.242 Hom.: 546

Bravo AF: 0.372

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.1
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs1079719; hg19: chr11-67351531; COSMIC: COSV66992955; COSMIC: COSV66992955;