10-94729240-T-A

Variant names:

• chr10-94729240-T-A
• rs7085563
• NM_000772.3:c.1150-4057T>A

Variant summary

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

The NM_000772.3(CYP2C18):​c.1150-4057T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,040 control chromosomes in the GnomAD database, including 3,537 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 0.20 (3537 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 4 publications found

Genes affected

CYP2C18 (HGNC:2620): (cytochrome P450 family 2 subfamily C member 18) 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 but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP2C17 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000276490 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.1150-4057T>A		intron_variant	Intron 7 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.973-4057T>A		intron_variant	Intron 6 of 7		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.1150-4057T>A		intron_variant	Intron 7 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.973-4057T>A		intron_variant	Intron 6 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.790-4057T>A		intron_variant	Intron 5 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30631 AN: 151922 Hom.: 3527 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.175

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30667 AN: 152040 Hom.: 3537 Cov.: 32 AF XY: 0.205 AC XY: 15260 AN XY: 74298

African (AFR) AF: 0.281 AC: 11667 AN: 41478

American (AMR) AF: 0.143 AC: 2186 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1927 AN: 5166

South Asian (SAS) AF: 0.336 AC: 1620 AN: 4816

European-Finnish (FIN) AF: 0.183 AC: 1937 AN: 10576

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10292 AN: 67956

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.174 Hom.: 337

Bravo AF: 0.198

Asia WGS AF: 0.358 AC: 1240 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.25
PhyloP100		-0.069
Mutation Taster		=100/0	polymorphism (auto)

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: rs7085563; hg19: chr10-96488997; COSMIC: COSV53675334;