rs4321325

Variant names:

• chr2-127193421-C-T
• rs4321325
• NM_001367502.1:c.1294-124G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001367502.1(CYP27C1):​c.1294-124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,093,934 control chromosomes in the GnomAD database, including 24,564 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 0.17 (2586 hom., cov: 32)
  • Exomes 𝑓: 0.21 (21978 hom.)
• Consequence: CYP27C1 NM_001367502.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP27C1	NM_001367502.1	c.1294-124G>A		intron_variant	Intron 7 of 8	ENST00000664447.2	NP_001354431.1
CYP27C1	NM_001001665.4	c.799-124G>A		intron_variant	Intron 6 of 7		NP_001001665.3
CYP27C1	NM_001367501.1	c.799-124G>A		intron_variant	Intron 6 of 7		NP_001354430.1
CYP27C1	XM_024452838.2	c.931-124G>A		intron_variant	Intron 7 of 8		XP_024308606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP27C1	ENST00000664447.2	c.1294-124G>A		intron_variant	Intron 7 of 8		NM_001367502.1	ENSP00000499243.1
CYP27C1	ENST00000335247.11	c.799-124G>A		intron_variant	Intron 6 of 7	1		ENSP00000334128.7
CYP27C1	ENST00000409327.2	c.799-124G>A		intron_variant	Intron 6 of 7	2		ENSP00000387198.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25659 AN: 152032 Hom.: 2586 Cov.: 32

Gnomad AFR AF: 0.0728

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0501

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.207 AC: 195085 AN: 941782 Hom.: 21978 AF XY: 0.211 AC XY: 100716 AN XY: 476780

Gnomad4 AFR exome AF: 0.0721

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.0381

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.243

Gnomad4 NFE exome AF: 0.215

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.169 AC: 25665 AN: 152152 Hom.: 2586 Cov.: 32 AF XY: 0.170 AC XY: 12625 AN XY: 74378

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.0502

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.172

Alfa AF: 0.186 Hom.: 353

Bravo AF: 0.151

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.35
DANN	Benign	0.78

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: rs4321325; hg19: chr2-127950997;