10-94695062-C-T

Variant names:

• chr10-94695062-C-T
• rs149450201
• NM_000772.3:c.627C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_000772.3(CYP2C18):​c.627C>T​(p.Ser209Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,612,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: CYP2C18 NM_000772.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138
• 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 10-94695062-C-T is Benign according to our data. Variant chr10-94695062-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.138 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.627C>T	p.Ser209Ser	synonymous_variant	Exon 4 of 9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.627C>T	p.Ser209Ser	synonymous_variant	Exon 4 of 8		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11	c.627C>T	p.Ser209Ser	synonymous_variant	Exon 4 of 9	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.627C>T	p.Ser209Ser	synonymous_variant	Exon 4 of 8	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.267C>T		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249944 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1459944 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 726278

African (AFR) AF: 0.000568 AC: 19 AN: 33424

American (AMR) AF: 0.0000448 AC: 2 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.0000349 AC: 3 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000200 AC: 1 AN: 4990

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111508

Other (OTH) AF: 0.000216 AC: 13 AN: 60262

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74428

African (AFR) AF: 0.000120 AC: 5 AN: 41544

American (AMR) AF: 0.000131 AC: 2 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000491

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CYP2C18: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.8
DANN	Benign	0.79
PhyloP100		-0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149450201; hg19: chr10-96454819; COSMIC: COSV53671810;