rs4811494

Variant names:

• chr20-54153445-C-T
• rs4811494
• XM_017027692.3:c.*10+3724G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-54153445-C-T
• chr20-54153445-C-A
• chr20-54153445-C-G

Variant summary

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

The ENST00000792273.1(ENSG00000286587):​n.155-14993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,002 control chromosomes in the GnomAD database, including 7,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7970 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000286587 ENST00000792273.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 5 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=-0.84).
• BP6: Variant 20-54153445-C-T is Benign according to our data. Variant chr20-54153445-C-T is described in ClinVar as Benign. ClinVar VariationId is 369356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000792273.1. 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.*1327G>A		downstream_gene	N/A	NP_000773.2	Q07973-1
	CYP24A1	NM_001424340.1		c.*1347G>A		downstream_gene	N/A	NP_001411269.1	Q07973-1
	CYP24A1	NM_001424341.1		c.*1499G>A		downstream_gene	N/A	NP_001411270.1	Q07973-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000286587	ENST00000792273.1		n.155-14993C>T		intron	N/A
	ENSG00000286587	ENST00000792274.1		n.145-14993C>T		intron	N/A
	ENSG00000286587	ENST00000792275.1		n.187-11169C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45611 AN: 151886 Hom.: 7964 Cov.: 33

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.272

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.300 AC: 45631 AN: 152002 Hom.: 7970 Cov.: 33 AF XY: 0.302 AC XY: 22421 AN XY: 74298

African (AFR) AF: 0.452 AC: 18704 AN: 41420

American (AMR) AF: 0.269 AC: 4107 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 861 AN: 3464

East Asian (EAS) AF: 0.592 AC: 3063 AN: 5174

South Asian (SAS) AF: 0.356 AC: 1713 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2152 AN: 10542

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14260 AN: 67974

Other (OTH) AF: 0.273 AC: 575 AN: 2110

Alfa AF: 0.215 Hom.: 1048

Bravo AF: 0.310

Asia WGS AF: 0.423 AC: 1459 AN: 3454

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Infantile hypercalcemia (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.63
DANN	Benign	0.77
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4811494; hg19: chr20-52769984;