chr11-67584356-G-C

Variant names:

• chr11-67584356-G-C
• rs8191446
• NM_000852.4:c.38-108G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000852.4(GSTP1):​c.38-108G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 729,950 control chromosomes in the GnomAD database, including 579 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 0.041 (416 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (163 hom.)
• Consequence: GSTP1 NM_000852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 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.38-108G>C		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.38-108G>C		intron	N/A	ENSP00000381607.3
	GSTP1	ENST00000494593.1	TSL:2	n.246G>C		non_coding_transcript_exon	Exon 2 of 3
	GSTP1	ENST00000398603.6	TSL:3	c.38-108G>C		intron	N/A	ENSP00000381604.1

Frequencies

GnomAD3 genomes AF: 0.0411 AC: 6248 AN: 152048 Hom.: 417 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.0317

GnomAD4 exome AF: 0.00533 AC: 3080 AN: 577782 Hom.: 163 Cov.: 8 AF XY: 0.00458 AC XY: 1381 AN XY: 301652

African (AFR) AF: 0.137 AC: 1996 AN: 14618

American (AMR) AF: 0.0127 AC: 250 AN: 19642

Ashkenazi Jewish (ASJ) AF: 0.0000684 AC: 1 AN: 14618

East Asian (EAS) AF: 0.0000313 AC: 1 AN: 31906

South Asian (SAS) AF: 0.000443 AC: 22 AN: 49648

European-Finnish (FIN) AF: 0.0000449 AC: 2 AN: 44536

Middle Eastern (MID) AF: 0.0157 AC: 38 AN: 2426

European-Non Finnish (NFE) AF: 0.00109 AC: 405 AN: 370480

Other (OTH) AF: 0.0122 AC: 365 AN: 29908

GnomAD4 genome AF: 0.0411 AC: 6255 AN: 152168 Hom.: 416 Cov.: 33 AF XY: 0.0396 AC XY: 2948 AN XY: 74384

African (AFR) AF: 0.139 AC: 5762 AN: 41496

American (AMR) AF: 0.0200 AC: 306 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 67994

Other (OTH) AF: 0.0313 AC: 66 AN: 2106

Alfa AF: 0.0244 Hom.: 27

Bravo AF: 0.0464

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.44
PhyloP100		-3.2
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: rs8191446; hg19: chr11-67351827;