rs11572078

chr10-95067362-TA-Tchr10-95067362-TA-TAAchr10-95067362-TA-TAAA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_000770.3(CYP2C8):c.332-6del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 19)
• Consequence: CYP2C8 NM_000770.3 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927

Genes affected

CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-95067362-TA-T is Benign according to our data. Variant chr10-95067362-TA-T is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C8	NM_000770.3	c.332-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000371270.6
CYP2C8	NM_001198853.1	c.122-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CYP2C8	NM_001198854.1	c.26-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
CYP2C8	NM_001198855.1	c.122-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C8	ENST00000371270.6	c.332-6del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000770.3	P1

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-96827119;