NM_000772.3:c.1149+3161C>T

Variant names:

• chr10-94727694-C-T
• rs7919273
• NM_000772.3:c.1149+3161C>T

Variant summary

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

The NM_000772.3(CYP2C18):​c.1149+3161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,824 control chromosomes in the GnomAD database, including 18,702 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 0.48 (18702 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 1 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.1149+3161C>T		intron_variant	Intron 7 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.972+3161C>T		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.1149+3161C>T		intron_variant	Intron 7 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.972+3161C>T		intron_variant	Intron 6 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.789+3161C>T		intron_variant	Intron 5 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73416 AN: 151712 Hom.: 18686 Cov.: 32

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.484 AC: 73474 AN: 151824 Hom.: 18702 Cov.: 32 AF XY: 0.484 AC XY: 35911 AN XY: 74210

African (AFR) AF: 0.633 AC: 26219 AN: 41390

American (AMR) AF: 0.337 AC: 5132 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2170 AN: 5166

South Asian (SAS) AF: 0.616 AC: 2965 AN: 4816

European-Finnish (FIN) AF: 0.419 AC: 4396 AN: 10492

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29577 AN: 67936

Other (OTH) AF: 0.460 AC: 966 AN: 2102

Alfa AF: 0.461 Hom.: 3018

Bravo AF: 0.478

Asia WGS AF: 0.533 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.25
PhyloP100		-2.7
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: rs7919273; hg19: chr10-96487451;