rs4809960

Variant names:

• chr20-54169534-T-C
• rs4809960
• NM_000782.5:c.640+58A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-54169534-T-C
• chr20-54169534-T-G

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.640+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,611,864 control chromosomes in the GnomAD database, including 45,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3455 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42057 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.83
• Publications: 51 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-54169534-T-C is Benign according to our data. Variant chr20-54169534-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.247 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.640+58A>G		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.640+58A>G		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.640+58A>G		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.640+58A>G		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.640+58A>G		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.214+58A>G		intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30758 AN: 152088 Hom.: 3450 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.238 AC: 347043 AN: 1459658 Hom.: 42057 AF XY: 0.239 AC XY: 173511 AN XY: 726140

African (AFR) AF: 0.112 AC: 3757 AN: 33448

American (AMR) AF: 0.223 AC: 9965 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 9097 AN: 26082

East Asian (EAS) AF: 0.237 AC: 9375 AN: 39628

South Asian (SAS) AF: 0.251 AC: 21633 AN: 86108

European-Finnish (FIN) AF: 0.184 AC: 9669 AN: 52598

Middle Eastern (MID) AF: 0.252 AC: 1452 AN: 5762

European-Non Finnish (NFE) AF: 0.241 AC: 267622 AN: 1111090

Other (OTH) AF: 0.240 AC: 14473 AN: 60294

GnomAD4 genome AF: 0.202 AC: 30772 AN: 152206 Hom.: 3455 Cov.: 32 AF XY: 0.200 AC XY: 14861 AN XY: 74418

African (AFR) AF: 0.116 AC: 4831 AN: 41538

American (AMR) AF: 0.220 AC: 3370 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1201 AN: 3466

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5176

South Asian (SAS) AF: 0.258 AC: 1247 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1906 AN: 10596

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16417 AN: 67994

Other (OTH) AF: 0.216 AC: 457 AN: 2112

Alfa AF: 0.233 Hom.: 7843

Bravo AF: 0.201

Asia WGS AF: 0.242 AC: 841 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	-0.91
CADD	Benign	0.039
DANN	Benign	0.29
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4809960; hg19: chr20-52786073; COSMIC: COSV53774641; COSMIC: COSV53774641;