rs116092201

Variant names:

• chr10-94694930-T-C
• rs116092201
• NM_000772.3:c.495T>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000772.3(CYP2C18):​c.495T>C​(p.Asp165Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00092 in 1,612,332 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (3 hom.)
• Consequence: CYP2C18 NM_000772.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-94694930-T-C is Benign according to our data. Variant chr10-94694930-T-C is described in ClinVar as [Benign]. Clinvar id is 712598.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00477 (727/152264) while in subpopulation AFR AF = 0.0163 (677/41540). AF 95% confidence interval is 0.0153. There are 7 homozygotes in GnomAd4. There are 338 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C18	NM_000772.3	c.495T>C	p.Asp165Asp	synonymous_variant	Exon 4 of 9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2	c.495T>C	p.Asp165Asp	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.495T>C	p.Asp165Asp	synonymous_variant	Exon 4 of 9	1	NM_000772.3	ENSP00000285979.6
CYP2C18	ENST00000339022.6	c.495T>C	p.Asp165Asp	synonymous_variant	Exon 4 of 8	1		ENSP00000341293.5
ENSG00000276490	ENST00000464755.1	n.135T>C		non_coding_transcript_exon_variant	Exon 2 of 14	2		ENSP00000483243.1

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152146 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.00141 AC: 355 AN: 251098 AF XY: 0.00108

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.000984

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000518 AC: 757 AN: 1460068 Hom.: 3 Cov.: 31 AF XY: 0.000458 AC XY: 333 AN XY: 726358

African (AFR) AF: 0.0161 AC: 538 AN: 33432

American (AMR) AF: 0.00123 AC: 55 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000212 AC: 1 AN: 4708

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111680

Other (OTH) AF: 0.00131 AC: 79 AN: 60266

GnomAD4 genome AF: 0.00477 AC: 727 AN: 152264 Hom.: 7 Cov.: 32 AF XY: 0.00454 AC XY: 338 AN XY: 74448

African (AFR) AF: 0.0163 AC: 677 AN: 41540

American (AMR) AF: 0.00196 AC: 30 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68020

Other (OTH) AF: 0.00332 AC: 7 AN: 2108

Alfa AF: 0.00278 Hom.: 1

Bravo AF: 0.00563

Asia WGS AF: 0.000867 AC: 3 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 11, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.9
DANN	Benign	0.75
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs116092201; hg19: chr10-96454687;