6-46649581-C-G

Position:

• chr6-46649581-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016593.5(CYP39A1):​c.177+2825G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,122 control chromosomes in the GnomAD database, including 4,299 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 0.22 (4299 hom., cov: 32)
• Consequence: CYP39A1 NM_016593.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

Genes affected

CYP39A1 (HGNC:17449): (cytochrome P450 family 39 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 endoplasmic reticulum protein is involved in the conversion of cholesterol to bile acids. Its substrates include the oxysterols 25-hydroxycholesterol, 27-hydroxycholesterol and 24-hydroxycholesterol. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP39A1	NM_016593.5	c.177+2825G>C		intron_variant		ENST00000275016.3	NP_057677.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP39A1	ENST00000275016.3	c.177+2825G>C		intron_variant		1	NM_016593.5	ENSP00000275016.2
CYP39A1	ENST00000619708.4	c.-165+2825G>C		intron_variant		1		ENSP00000477769.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33408 AN: 152002 Hom.: 4296 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.220 AC: 33446 AN: 152122 Hom.: 4299 Cov.: 32 AF XY: 0.223 AC XY: 16548 AN XY: 74372

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.212

Alfa AF: 0.0714 Hom.: 91

Bravo AF: 0.230

Asia WGS AF: 0.287 AC: 996 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498769; hg19: chr6-46617318;