rs6022999

Variant names:

• chr20-54171474-A-G
• rs6022999
• NM_000782.5:c.543+103T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-54171474-A-G
• chr20-54171474-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.543+103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,605,494 control chromosomes in the GnomAD database, including 58,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (11772 hom., cov: 31)
  • Exomes 𝑓: 0.24 (46625 hom.)
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.316
• Publications: 42 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=-0.86).
• BP6: Variant 20-54171474-A-G is Benign according to our data. Variant chr20-54171474-A-G is described in ClinVar as Benign. ClinVar VariationId is 1256746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 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.543+103T>C		intron	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.543+103T>C		intron	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.543+103T>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.543+103T>C		intron	N/A	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.543+103T>C		intron	N/A	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.117+103T>C		intron	N/A	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53191 AN: 151790 Hom.: 11723 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.334

GnomAD4 exome AF: 0.242 AC: 351281 AN: 1453586 Hom.: 46625 AF XY: 0.240 AC XY: 173352 AN XY: 722834

African (AFR) AF: 0.658 AC: 21839 AN: 33186

American (AMR) AF: 0.184 AC: 8190 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 9002 AN: 26046

East Asian (EAS) AF: 0.226 AC: 8943 AN: 39570

South Asian (SAS) AF: 0.184 AC: 15765 AN: 85710

European-Finnish (FIN) AF: 0.247 AC: 12934 AN: 52376

Middle Eastern (MID) AF: 0.348 AC: 1485 AN: 4268

European-Non Finnish (NFE) AF: 0.232 AC: 257396 AN: 1108006

Other (OTH) AF: 0.263 AC: 15727 AN: 59908

GnomAD4 genome AF: 0.351 AC: 53289 AN: 151908 Hom.: 11772 Cov.: 31 AF XY: 0.347 AC XY: 25769 AN XY: 74234

African (AFR) AF: 0.641 AC: 26544 AN: 41412

American (AMR) AF: 0.247 AC: 3777 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1183 AN: 3466

East Asian (EAS) AF: 0.209 AC: 1074 AN: 5150

South Asian (SAS) AF: 0.173 AC: 835 AN: 4814

European-Finnish (FIN) AF: 0.262 AC: 2767 AN: 10544

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16040 AN: 67940

Other (OTH) AF: 0.335 AC: 705 AN: 2106

Alfa AF: 0.265 Hom.: 10091

Bravo AF: 0.363

Asia WGS AF: 0.208 AC: 726 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	-0.86
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-0.32
PromoterAI		-0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6022999; hg19: chr20-52788013; COSMIC: COSV53776027; COSMIC: COSV53776027;