chr20-54162530-T-G

Variant names:

• chr20-54162530-T-G
• rs3831062
• NM_000782.5:c.990+187A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000782.5(CYP24A1):​c.990+187A>C 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 0.0067 (11 hom., cov: 17)
  • Exomes 𝑓: 0.00066 (3 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 1 publications found

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, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00666 (568/85302) while in subpopulation AFR AF = 0.0204 (440/21536). AF 95% confidence interval is 0.0189. There are 11 homozygotes in GnomAd4. There are 264 alleles in the male GnomAd4 subpopulation. Median coverage is 17. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	NM_000782.5	MANE Select	c.990+187A>C		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.990+187A>C		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.990+187A>C		intron	N/A	NP_001411270.1	Q07973-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.990+187A>C		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.990+187A>C		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.564+187A>C		intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 569 AN: 85260 Hom.: 11 Cov.: 17

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.00532

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.00250

Gnomad EAS AF: 0.00583

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.000437

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00702

GnomAD4 exome AF: 0.000658 AC: 291 AN: 442136 Hom.: 3 Cov.: 4 AF XY: 0.000680 AC XY: 160 AN XY: 235416

African (AFR) AF: 0.0109 AC: 136 AN: 12496

American (AMR) AF: 0.000614 AC: 15 AN: 24414

Ashkenazi Jewish (ASJ) AF: 0.000216 AC: 3 AN: 13908

East Asian (EAS) AF: 0.000462 AC: 13 AN: 28110

South Asian (SAS) AF: 0.000661 AC: 32 AN: 48442

European-Finnish (FIN) AF: 0.000146 AC: 4 AN: 27446

Middle Eastern (MID) AF: 0.000470 AC: 1 AN: 2126

European-Non Finnish (NFE) AF: 0.000246 AC: 64 AN: 260224

Other (OTH) AF: 0.000921 AC: 23 AN: 24970

GnomAD4 genome AF: 0.00666 AC: 568 AN: 85302 Hom.: 11 Cov.: 17 AF XY: 0.00635 AC XY: 264 AN XY: 41544

African (AFR) AF: 0.0204 AC: 440 AN: 21536

American (AMR) AF: 0.00247 AC: 21 AN: 8516

Ashkenazi Jewish (ASJ) AF: 0.00250 AC: 5 AN: 2002

East Asian (EAS) AF: 0.00583 AC: 11 AN: 1888

South Asian (SAS) AF: 0.00559 AC: 12 AN: 2148

European-Finnish (FIN) AF: 0.000437 AC: 3 AN: 6864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.00162 AC: 66 AN: 40644

Other (OTH) AF: 0.00697 AC: 8 AN: 1148

Alfa AF: 0.00264 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.42
DANN	Benign	0.36
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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.

Other links and lift over

dbSNP: rs3831062; hg19: chr20-52779069; COSMIC: COSV53773233; COSMIC: COSV53773233;