2-203300448-T-C

Variant names:

• chr2-203300448-T-C
• rs11888559
• NM_177538.3:c.*3540T>C

Variant summary

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

The NM_177538.3(CYP20A1):​c.*3540T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,142 control chromosomes in the GnomAD database, including 53,647 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 0.82 (53647 hom., cov: 33)
• Consequence: CYP20A1 NM_177538.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 18 publications found

Genes affected

CYP20A1 (HGNC:20576): (cytochrome P450 family 20 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein lacks one amino acid of the conserved heme binding site. It also lacks the conserved I-helix motif AGX(D,E)T, suggesting that its substrate may carry its own oxygen. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177538.3. 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
	CYP20A1	NM_177538.3	MANE Select	c.*3540T>C		3_prime_UTR	Exon 13 of 13	NP_803882.1	Q6UW02-1
	CYP20A1	NM_001371695.1		c.*3540T>C		3_prime_UTR	Exon 13 of 13	NP_001358624.1	E9PHG5
	CYP20A1	NM_001371696.1		c.*3540T>C		3_prime_UTR	Exon 11 of 11	NP_001358625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP20A1	ENST00000356079.9	TSL:1 MANE Select	c.*3540T>C		3_prime_UTR	Exon 13 of 13	ENSP00000348380.4	Q6UW02-1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124492 AN: 152024 Hom.: 53639 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.874

Gnomad ASJ AF: 0.963

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.868

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.950

Gnomad OTH AF: 0.850

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

GnomAD4 genome AF: 0.819 AC: 124544 AN: 152142 Hom.: 53647 Cov.: 33 AF XY: 0.821 AC XY: 61018 AN XY: 74366

African (AFR) AF: 0.522 AC: 21639 AN: 41446

American (AMR) AF: 0.874 AC: 13342 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.963 AC: 3342 AN: 3472

East Asian (EAS) AF: 0.834 AC: 4323 AN: 5182

South Asian (SAS) AF: 0.867 AC: 4192 AN: 4834

European-Finnish (FIN) AF: 0.956 AC: 10118 AN: 10584

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.950 AC: 64631 AN: 68032

Other (OTH) AF: 0.851 AC: 1800 AN: 2114

Alfa AF: 0.908 Hom.: 267139

Bravo AF: 0.798

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs11888559; hg19: chr2-204165171;