10-94720472-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000772.3(CYP2C18):c.896C>T(p.Thr299Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,613,328 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (4 hom.)
• Consequence: CYP2C18 NM_000772.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.01

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018897504).
• BP6: Variant 10-94720472-C-T is Benign according to our data. Variant chr10-94720472-C-T is described in ClinVar as [Benign]. Clinvar id is 713979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP2C18	NM_000772.3	c.896C>T	p.Thr299Ile	missense_variant	6/9	ENST00000285979.11
CYP2C18	NM_001128925.2	c.719C>T	p.Thr240Ile	missense_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP2C18	ENST00000285979.11	c.896C>T	p.Thr299Ile	missense_variant	6/9	1	NM_000772.3	P1
CYP2C18	ENST00000339022.6	c.719C>T	p.Thr240Ile	missense_variant	5/8	1

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152122 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000147

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000833 AC: 209 AN: 250866 Hom.: 0 AF XY: 0.000598 AC XY: 81 AN XY: 135562

Gnomad AFR exome AF: 0.0113

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000381 AC: 557 AN: 1461088 Hom.: 4 Cov.: 30 AF XY: 0.000305 AC XY: 222 AN XY: 726878

Gnomad4 AFR exome AF: 0.0133

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00355 AC: 540 AN: 152240 Hom.: 2 Cov.: 32 AF XY: 0.00345 AC XY: 257 AN XY: 74426

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000667 Hom.: 0

Bravo AF: 0.00419

ESP6500AA AF: 0.0116 AC: 51

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00101 AC: 123

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.25	T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.87	D;D
MetaRNN	Benign	0.019	T;T
MetaSVM	Uncertain	0.042	D
MutationAssessor	Pathogenic	3.1	M;.
MutationTaster	Benign	0.78	D;D
PROVEAN	Pathogenic	-5.0	D;D
REVEL	Uncertain	0.48
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.027	D;D
Polyphen		0.99	D;.
Vest4		0.44
MVP		0.80
MPC		0.12
ClinPred		0.13	T
GERP RS		4.2
Varity_R		0.31
gMVP		0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs60181876; hg19: chr10-96480229;