rs6127119

Variant names:

• chr20-54162543-C-A
• rs6127119
• NM_000782.5:c.990+174G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-54162543-C-A
• chr20-54162543-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000782.5(CYP24A1):​c.990+174G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 25)
  • Exomes 𝑓: 0.0000044 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP24A1 NM_000782.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	NM_000782.5	MANE Select	c.990+174G>T		intron	N/A	NP_000773.2
	CYP24A1	NM_001424340.1		c.990+174G>T		intron	N/A	NP_001411269.1
	CYP24A1	NM_001424341.1		c.990+174G>T		intron	N/A	NP_001411270.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP24A1	ENST00000216862.8	TSL:1 MANE Select	c.990+174G>T		intron	N/A	ENSP00000216862.3
	CYP24A1	ENST00000395955.7	TSL:1	c.990+174G>T		intron	N/A	ENSP00000379285.3
	CYP24A1	ENST00000395954.3	TSL:1	c.564+174G>T		intron	N/A	ENSP00000379284.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 139914 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000441 AC: 2 AN: 453896 Hom.: 1 Cov.: 4 AF XY: 0.00000827 AC XY: 2 AN XY: 241972

African (AFR) AF: 0.00 AC: 0 AN: 13016

American (AMR) AF: 0.00 AC: 0 AN: 26302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14516

East Asian (EAS) AF: 0.0000723 AC: 2 AN: 27674

South Asian (SAS) AF: 0.00 AC: 0 AN: 49796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2332

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 265612

Other (OTH) AF: 0.00 AC: 0 AN: 25588

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 139914 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 67594

African (AFR) AF: 0.00 AC: 0 AN: 37214

American (AMR) AF: 0.00 AC: 0 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3296

East Asian (EAS) AF: 0.00 AC: 0 AN: 4650

South Asian (SAS) AF: 0.00 AC: 0 AN: 4192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64194

Other (OTH) AF: 0.00 AC: 0 AN: 1886

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.28

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: rs6127119; hg19: chr20-52779082;