2-127204917-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP27C1	NM_001367502.1	c.473+983A>G		intron_variant	Intron 2 of 8	ENST00000664447.2	NP_001354431.1
CYP27C1	NM_001001665.4	c.-23+742A>G		intron_variant	Intron 1 of 7		NP_001001665.3
CYP27C1	NM_001367501.1	c.-22-1346A>G		intron_variant	Intron 1 of 7		NP_001354430.1
CYP27C1	XM_024452838.2	c.110+983A>G		intron_variant	Intron 2 of 8		XP_024308606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP27C1	ENST00000664447.2	c.473+983A>G		intron_variant	Intron 2 of 8		NM_001367502.1	ENSP00000499243.1
CYP27C1	ENST00000335247.11	c.-23+742A>G		intron_variant	Intron 1 of 7	1		ENSP00000334128.7
CYP27C1	ENST00000409327.2	c.-22-1346A>G		intron_variant	Intron 1 of 7	2		ENSP00000387198.1

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

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.905

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.697

Alfa AF: 0.676 Hom.: 45596

Bravo AF: 0.701

Asia WGS AF: 0.791 AC: 2748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs7585314; hg19: chr2-127962493;