10-94728712-C-T

Variant names:

• chr10-94728712-C-T
• rs932809
• NM_000772.3:c.1149+4179C>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+4179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 479,746 control chromosomes in the GnomAD database, including 6,443 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 0.17 (2505 hom., cov: 32)
  • Exomes 𝑓: 0.15 (3938 hom.)
• Consequence: CYP2C18 NM_000772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000772.3. 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
	CYP2C18	NM_000772.3	MANE Select	c.1149+4179C>T		intron	N/A	NP_000763.1
	CYP2C18	NM_001128925.2		c.972+4179C>T		intron	N/A	NP_001122397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP2C18	ENST00000285979.11	TSL:1 MANE Select	c.1149+4179C>T		intron	N/A	ENSP00000285979.6
	CYP2C18	ENST00000339022.6	TSL:1	c.972+4179C>T		intron	N/A	ENSP00000341293.5
	ENSG00000276490	ENST00000464755.1	TSL:2	n.789+4179C>T		intron	N/A	ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26221 AN: 151606 Hom.: 2500 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.153

GnomAD4 exome AF: 0.146 AC: 47989 AN: 328024 Hom.: 3938 AF XY: 0.147 AC XY: 22965 AN XY: 156014

African (AFR) AF: 0.199 AC: 1166 AN: 5850

American (AMR) AF: 0.0901 AC: 31 AN: 344

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 248 AN: 1998

East Asian (EAS) AF: 0.289 AC: 381 AN: 1320

South Asian (SAS) AF: 0.310 AC: 1901 AN: 6130

European-Finnish (FIN) AF: 0.113 AC: 12 AN: 106

Middle Eastern (MID) AF: 0.124 AC: 80 AN: 646

European-Non Finnish (NFE) AF: 0.141 AC: 42437 AN: 301044

Other (OTH) AF: 0.164 AC: 1733 AN: 10586

GnomAD4 genome AF: 0.173 AC: 26243 AN: 151722 Hom.: 2505 Cov.: 32 AF XY: 0.177 AC XY: 13119 AN XY: 74134

African (AFR) AF: 0.196 AC: 8095 AN: 41386

American (AMR) AF: 0.133 AC: 2023 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.313 AC: 1607 AN: 5140

South Asian (SAS) AF: 0.330 AC: 1584 AN: 4798

European-Finnish (FIN) AF: 0.184 AC: 1932 AN: 10490

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

European-Non Finnish (NFE) AF: 0.148 AC: 10020 AN: 67912

Other (OTH) AF: 0.157 AC: 331 AN: 2104

Alfa AF: 0.153 Hom.: 2413

Bravo AF: 0.167

Asia WGS AF: 0.305 AC: 1055 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.31
PhyloP100		-0.95
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: rs932809; hg19: chr10-96488469;