chr11-67584060-G-A

Variant names:

• chr11-67584060-G-A
• rs1079719
• NM_000852.4:c.2-74G>A

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.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
• 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=-0.82).
• BP6: Variant 11-67584060-G-A is Benign according to our data. Variant chr11-67584060-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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.2-74G>A		intron	N/A	NP_000843.1	P09211

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTP1	ENST00000398606.10	TSL:1 MANE Select	c.2-74G>A		intron	N/A	ENSP00000381607.3	P09211
	GSTP1	ENST00000495996.2	TSL:2	c.2-74G>A		intron	N/A	ENSP00000484686.2
	GSTP1	ENST00000906565.1		c.2-74G>A		intron	N/A	ENSP00000576624.1

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

African (AFR) AF: 0.392 AC: 11113 AN: 28368

American (AMR) AF: 0.235 AC: 9090 AN: 38604

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 6155 AN: 22930

East Asian (EAS) AF: 0.159 AC: 5714 AN: 35992

South Asian (SAS) AF: 0.330 AC: 24781 AN: 75196

European-Finnish (FIN) AF: 0.348 AC: 17401 AN: 50052

Middle Eastern (MID) AF: 0.393 AC: 1407 AN: 3580

European-Non Finnish (NFE) AF: 0.473 AC: 381383 AN: 806660

Other (OTH) AF: 0.404 AC: 19504 AN: 48274

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

African (AFR) AF: 0.390 AC: 16002 AN: 41048

American (AMR) AF: 0.278 AC: 4242 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3464

East Asian (EAS) AF: 0.159 AC: 813 AN: 5102

South Asian (SAS) AF: 0.302 AC: 1433 AN: 4752

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10562

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28911 AN: 67806

Other (OTH) AF: 0.371 AC: 780 AN: 2104

Alfa AF: 0.242 Hom.: 546

Bravo AF: 0.372

ClinVar

ClinVar submissions

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	-0.82
CADD	Benign	8.1
DANN	Benign	0.94
PhyloP100		0.60
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=9/91	disease causing

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