chr2-127204917-T-C

Variant names:

• chr2-127204917-T-C
• rs7585314
• NM_001367502.1:c.473+983A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367502.1(CYP27C1):​c.473+983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,068 control chromosomes in the GnomAD database, including 36,714 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 0.69 (36714 hom., cov: 33)
• Consequence: CYP27C1 NM_001367502.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525
• Publications: 14 publications found

Genes affected

CYP27C1 (HGNC:33480): (cytochrome P450 family 27 subfamily C member 1) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367502.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27C1	NM_001367502.1	MANE Select	c.473+983A>G		intron	N/A	NP_001354431.1	A0A7N4I3A3
	CYP27C1	NM_001001665.4		c.-23+742A>G		intron	N/A	NP_001001665.3	Q4G0S4-1
	CYP27C1	NM_001367501.1		c.-22-1346A>G		intron	N/A	NP_001354430.1	Q4G0S4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP27C1	ENST00000664447.2	MANE Select	c.473+983A>G		intron	N/A	ENSP00000499243.1	A0A7N4I3A3
	CYP27C1	ENST00000335247.11	TSL:1	c.-23+742A>G		intron	N/A	ENSP00000334128.7	Q4G0S4-1
	CYP27C1	ENST00000911450.1		c.473+983A>G		intron	N/A	ENSP00000581514.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105143 AN: 151952 Hom.: 36673 Cov.: 33

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.692 AC: 105242 AN: 152068 Hom.: 36714 Cov.: 33 AF XY: 0.696 AC XY: 51742 AN XY: 74316

African (AFR) AF: 0.678 AC: 28111 AN: 41458

American (AMR) AF: 0.783 AC: 11975 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2451 AN: 3472

East Asian (EAS) AF: 0.905 AC: 4673 AN: 5162

South Asian (SAS) AF: 0.610 AC: 2939 AN: 4820

European-Finnish (FIN) AF: 0.723 AC: 7645 AN: 10572

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45278 AN: 67966

Other (OTH) AF: 0.697 AC: 1472 AN: 2112

Alfa AF: 0.677 Hom.: 58019

Bravo AF: 0.701

Asia WGS AF: 0.791 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.30
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs7585314; hg19: chr2-127962493;