NM_001367502.1:c.1294-124G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.88).
• 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

African (AFR) AF: 0.0721 AC: 1617 AN: 22438

American (AMR) AF: 0.0986 AC: 2931 AN: 29722

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 4407 AN: 19016

East Asian (EAS) AF: 0.0381 AC: 1303 AN: 34234

South Asian (SAS) AF: 0.282 AC: 17677 AN: 62694

European-Finnish (FIN) AF: 0.243 AC: 9783 AN: 40190

Middle Eastern (MID) AF: 0.294 AC: 890 AN: 3024

European-Non Finnish (NFE) AF: 0.215 AC: 147984 AN: 688006

Other (OTH) AF: 0.200 AC: 8493 AN: 42458

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

African (AFR) AF: 0.0729 AC: 3027 AN: 41542

American (AMR) AF: 0.129 AC: 1975 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3470

East Asian (EAS) AF: 0.0502 AC: 260 AN: 5178

South Asian (SAS) AF: 0.279 AC: 1343 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2640 AN: 10578

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14888 AN: 67958

Other (OTH) AF: 0.172 AC: 364 AN: 2114

Alfa AF: 0.197 Hom.: 5267

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
PhyloP100		-1.7
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: rs4321325; hg19: chr2-127950997;