rs2274130

Variant names:

• chr20-54158062-A-G
• rs2274130
• NM_000782.5:c.1236+24T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-54158062-A-G
• chr20-54158062-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000782.5(CYP24A1):​c.1236+24T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 1,612,048 control chromosomes in the GnomAD database, including 53,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7335 hom., cov: 33)
  • Exomes 𝑓: 0.24 (46462 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29
• Publications: 10 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: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
• autosomal recessive infantile hypercalcemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 20-54158062-A-G is Benign according to our data. Variant chr20-54158062-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

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.1236+24T>C		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.1236+24T>C		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.1236+24T>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.1236+24T>C		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.1236+24T>C		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.810+24T>C		intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44180 AN: 152012 Hom.: 7328 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.263

GnomAD2 exomes AF: 0.280 AC: 69724 AN: 249190 AF XY: 0.277

Gnomad AFR exome AF: 0.416

Gnomad AMR exome AF: 0.273

Gnomad ASJ exome AF: 0.235

Gnomad EAS exome AF: 0.616

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.212

Gnomad OTH exome AF: 0.251

GnomAD4 exome AF: 0.240 AC: 349754 AN: 1459918 Hom.: 46462 Cov.: 34 AF XY: 0.241 AC XY: 175148 AN XY: 726314

African (AFR) AF: 0.425 AC: 14224 AN: 33470

American (AMR) AF: 0.270 AC: 12049 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 6111 AN: 26110

East Asian (EAS) AF: 0.592 AC: 23482 AN: 39686

South Asian (SAS) AF: 0.341 AC: 29372 AN: 86228

European-Finnish (FIN) AF: 0.207 AC: 10781 AN: 52020

Middle Eastern (MID) AF: 0.209 AC: 1204 AN: 5760

European-Non Finnish (NFE) AF: 0.213 AC: 236546 AN: 1111588

Other (OTH) AF: 0.265 AC: 15985 AN: 60350

GnomAD4 genome AF: 0.291 AC: 44209 AN: 152130 Hom.: 7335 Cov.: 33 AF XY: 0.293 AC XY: 21826 AN XY: 74390

African (AFR) AF: 0.416 AC: 17255 AN: 41472

American (AMR) AF: 0.273 AC: 4177 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 795 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3130 AN: 5162

South Asian (SAS) AF: 0.354 AC: 1710 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2155 AN: 10596

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14233 AN: 68002

Other (OTH) AF: 0.264 AC: 559 AN: 2114

Alfa AF: 0.238 Hom.: 1875

Bravo AF: 0.300

Asia WGS AF: 0.432 AC: 1502 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.043
DANN	Benign	0.38
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2274130;

hg19: chr20-52774601;