10-94700015-G-T

Variant names:

• chr10-94700015-G-T
• rs4600139
• NM_000772.3:c.642+4938G>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.642+4938G>T variant causes a intron change. The variant allele was found at a frequency of 0.283 in 152,050 control chromosomes in the GnomAD database, including 7,419 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 0.28 (7419 hom., cov: 32)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: No conservation score assigned
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.642+4938G>T		intron_variant	Intron 4 of 8	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.642+4938G>T		intron_variant	Intron 4 of 7		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.642+4938G>T		intron_variant	Intron 4 of 8	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.642+4938G>T		intron_variant	Intron 4 of 7	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.282+4938G>T		intron_variant	Intron 2 of 13	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43052 AN: 151932 Hom.: 7408 Cov.: 32

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.283 AC: 43076 AN: 152050 Hom.: 7419 Cov.: 32 AF XY: 0.287 AC XY: 21356 AN XY: 74312

African (AFR) AF: 0.0868 AC: 3605 AN: 41514

American (AMR) AF: 0.431 AC: 6573 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3470

East Asian (EAS) AF: 0.185 AC: 958 AN: 5170

South Asian (SAS) AF: 0.228 AC: 1097 AN: 4818

European-Finnish (FIN) AF: 0.449 AC: 4734 AN: 10536

Middle Eastern (MID) AF: 0.219 AC: 64 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23969 AN: 67960

Other (OTH) AF: 0.288 AC: 609 AN: 2112

Alfa AF: 0.183 Hom.: 428

Bravo AF: 0.276

Asia WGS AF: 0.185 AC: 643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.64
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: rs4600139; hg19: chr10-96459772;