Genetic Variant CYP27C1:c.1294-124G>A (chr2-127193421-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.66

Publications

8 publications found

Variant links:

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]

CYP27C1 links:

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ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP27C1	NM_001367502.1	MANE Select	c.1294-124G>A	intron	N/A	NP_001354431.1	A0A7N4I3A3
CYP27C1	NM_001001665.4		c.799-124G>A	intron	N/A	NP_001001665.3	Q4G0S4-1
CYP27C1	NM_001367501.1		c.799-124G>A	intron	N/A	NP_001354430.1	Q4G0S4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP27C1	ENST00000664447.2	MANE Select	c.1294-124G>A	intron	N/A	ENSP00000499243.1	A0A7N4I3A3
CYP27C1	ENST00000335247.11	TSL:1	c.799-124G>A	intron	N/A	ENSP00000334128.7	Q4G0S4-1
CYP27C1	ENST00000911450.1		c.1084-124G>A	intron	N/A	ENSP00000581514.1

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25659

AN:

152032

Hom.:

2586

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8003

16007

24010

32014

40017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4198

8396

12594

16792

20990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.169

AC:

25665

AN:

152152

Hom.:

2586

Cov.:

AF XY:

0.170

AC XY:

12625

AN XY:

74378

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14888

AN:

67958

Other (OTH)

AF:

0.172

AC:

364

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1084

2168

3252

4336

5420

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.35

(source)

DANN

Benign

0.78

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over