Genetic Variant CYP24A1:c.990+174G>T (chr20-54162543-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is . The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000782.5(CYP24A1):c.990+174G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000044 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CYP24A1
NM_000782.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.279

Publications

0 publications found

Variant links:

Genes affected

CYP24A1 (HGNC:2602): (cytochrome P450 family 24 subfamily A 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. This mitochondrial protein initiates the degradation of 1,25-dihydroxyvitamin D3, the physiologically active form of vitamin D3, by hydroxylation of the side chain. In regulating the level of vitamin D3, this enzyme plays a role in calcium homeostasis and the vitamin D endocrine system. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP24A1 Gene-Disease associations (from GenCC):

hypercalcemia, infantile, 1
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
autosomal recessive infantile hypercalcemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CYP24A1 links:

ENSG00000286587 (HGNC:):

ENSG00000286587 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000782.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP24A1	NM_000782.5	MANE Select	c.990+174G>T	intron	N/A	NP_000773.2	Q07973-1
CYP24A1	NM_001424340.1		c.990+174G>T	intron	N/A	NP_001411269.1	Q07973-1
CYP24A1	NM_001424341.1		c.990+174G>T	intron	N/A	NP_001411270.1	Q07973-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.990+174G>T	intron	N/A	ENSP00000216862.3	Q07973-1
CYP24A1	ENST00000395955.7	TSL:1	c.990+174G>T	intron	N/A	ENSP00000379285.3	Q07973-2
CYP24A1	ENST00000395954.3	TSL:1	c.564+174G>T	intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

139914

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000441

AC:

AN:

453896

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

241972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

13016

American (AMR)

AF:

0.00

AC:

AN:

26302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14516

East Asian (EAS)

AF:

0.0000723

AC:

AN:

27674

South Asian (SAS)

AF:

0.00

AC:

AN:

49796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2332

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

265612

Other (OTH)

AF:

0.00

AC:

AN:

25588

Age Distribution

Exome Hom

Variant carriers

<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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

139914

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67594

African (AFR)

AF:

0.00

AC:

AN:

37214

American (AMR)

AF:

0.00

AC:

AN:

13868

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

4650

South Asian (SAS)

AF:

0.00

AC:

AN:

4192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9462

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

64194

Other (OTH)

AF:

0.00

AC:

AN:

1886

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.2

(source)

DANN

Benign

0.59

PhyloP100

-0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over