rs6127112

Variant names:

• chr20-54145114-G-A
• rs6127112
• XM_017027692.3:c.*1364C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017027692.3(CYP24A1):​c.*1364C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 152,018 control chromosomes in the GnomAD database, including 672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (672 hom., cov: 31)
• Consequence: CYP24A1 XM_017027692.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP24A1	XM_017027692.3	c.*1364C>T		3_prime_UTR_variant	Exon 12 of 12		XP_016883181.1
CYP24A1	XM_047439938.1	c.*1364C>T		3_prime_UTR_variant	Exon 11 of 11		XP_047295894.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286587	ENST00000792273.1	n.155-23324G>A		intron_variant	Intron 2 of 3
ENSG00000286587	ENST00000792274.1	n.145-23324G>A		intron_variant	Intron 2 of 6
ENSG00000286587	ENST00000792275.1	n.187-19500G>A		intron_variant	Intron 1 of 2
ENSG00000286587	ENST00000792276.1	n.125+21197G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12947 AN: 151900 Hom.: 674 Cov.: 31

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0735

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0610

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0995

Gnomad OTH AF: 0.0906

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0852 AC: 12950 AN: 152018 Hom.: 672 Cov.: 31 AF XY: 0.0858 AC XY: 6378 AN XY: 74330

African (AFR) AF: 0.0461 AC: 1913 AN: 41462

American (AMR) AF: 0.0734 AC: 1121 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 510 AN: 3472

East Asian (EAS) AF: 0.148 AC: 767 AN: 5178

South Asian (SAS) AF: 0.206 AC: 993 AN: 4820

European-Finnish (FIN) AF: 0.0610 AC: 642 AN: 10524

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0995 AC: 6763 AN: 67968

Other (OTH) AF: 0.0916 AC: 193 AN: 2108

Alfa AF: 0.0994 Hom.: 596

Bravo AF: 0.0812

Asia WGS AF: 0.168 AC: 582 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.48
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs6127112; hg19: chr20-52761653;