rs6068816

Variant names:

• chr20-54164552-C-T
• rs6068816
• NM_000782.5:c.744G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-54164552-C-T
• chr20-54164552-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000782.5(CYP24A1):​c.744G>A​(p.Thr248Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,614,026 control chromosomes in the GnomAD database, including 12,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (1008 hom., cov: 32)
  • Exomes 𝑓: 0.11 (11261 hom.)
• Consequence: CYP24A1 NM_000782.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.32
• Publications: 84 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 20-54164552-C-T is Benign according to our data. Variant chr20-54164552-C-T is described in ClinVar as Benign. ClinVar VariationId is 338825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.32 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 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.744G>A	p.Thr248Thr	synonymous	Exon 6 of 12	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.744G>A	p.Thr248Thr	synonymous	Exon 6 of 12	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.744G>A	p.Thr248Thr	synonymous	Exon 6 of 12	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.744G>A	p.Thr248Thr	synonymous	Exon 6 of 12	ENSP00000216862.3	Q07973-1
	CYP24A1	ENST00000395955.7	TSL:1	c.744G>A	p.Thr248Thr	synonymous	Exon 6 of 11	ENSP00000379285.3	Q07973-2
	CYP24A1	ENST00000395954.3	TSL:1	c.318G>A	p.Thr106Thr	synonymous	Exon 4 of 10	ENSP00000379284.3	Q07973-3

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14411 AN: 152056 Hom.: 1007 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0967

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.0652

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.124 AC: 31139 AN: 251404 AF XY: 0.126

Gnomad AFR exome AF: 0.0398

Gnomad AMR exome AF: 0.103

Gnomad ASJ exome AF: 0.119

Gnomad EAS exome AF: 0.367

Gnomad FIN exome AF: 0.0734

Gnomad NFE exome AF: 0.104

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.113 AC: 165407 AN: 1461852 Hom.: 11261 Cov.: 33 AF XY: 0.115 AC XY: 83343 AN XY: 727230

African (AFR) AF: 0.0385 AC: 1290 AN: 33480

American (AMR) AF: 0.103 AC: 4619 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 3056 AN: 26134

East Asian (EAS) AF: 0.380 AC: 15074 AN: 39698

South Asian (SAS) AF: 0.158 AC: 13640 AN: 86258

European-Finnish (FIN) AF: 0.0760 AC: 4058 AN: 53418

Middle Eastern (MID) AF: 0.129 AC: 741 AN: 5766

European-Non Finnish (NFE) AF: 0.104 AC: 115657 AN: 1111984

Other (OTH) AF: 0.120 AC: 7272 AN: 60390

GnomAD4 genome AF: 0.0947 AC: 14415 AN: 152174 Hom.: 1008 Cov.: 32 AF XY: 0.0958 AC XY: 7129 AN XY: 74380

African (AFR) AF: 0.0408 AC: 1696 AN: 41528

American (AMR) AF: 0.0969 AC: 1482 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 354 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1885 AN: 5156

South Asian (SAS) AF: 0.172 AC: 831 AN: 4822

European-Finnish (FIN) AF: 0.0652 AC: 690 AN: 10584

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7065 AN: 68002

Other (OTH) AF: 0.103 AC: 217 AN: 2114

Alfa AF: 0.104 Hom.: 3874

Bravo AF: 0.0945

EpiCase AF: 0.100

EpiControl AF: 0.110

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Hypercalcemia, infantile, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.23
DANN	Benign	0.65
PhyloP100		-4.3
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: rs6068816; hg19: chr20-52781091; COSMIC: COSV107247184; COSMIC: COSV107247184;