6-46649581-C-G

Variant names:

• chr6-46649581-C-G
• rs10498769
• NM_016593.5:c.177+2825G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016593.5. 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
	CYP39A1	NM_016593.5	MANE Select	c.177+2825G>C		intron	N/A	NP_057677.2
	CYP39A1	NM_001278738.2		c.177+2825G>C		intron	N/A	NP_001265667.1
	CYP39A1	NM_001278739.2		c.-165+2825G>C		intron	N/A	NP_001265668.1	A0A087WTD2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP39A1	ENST00000275016.3	TSL:1 MANE Select	c.177+2825G>C		intron	N/A	ENSP00000275016.2	Q9NYL5
	CYP39A1	ENST00000619708.4	TSL:1	c.-165+2825G>C		intron	N/A	ENSP00000477769.1	A0A087WTD2
	CYP39A1	ENST00000889608.1		c.177+2825G>C		intron	N/A	ENSP00000559667.1

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

African (AFR) AF: 0.333 AC: 13795 AN: 41458

American (AMR) AF: 0.287 AC: 4384 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3468

East Asian (EAS) AF: 0.173 AC: 898 AN: 5178

South Asian (SAS) AF: 0.339 AC: 1638 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1359 AN: 10592

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9941 AN: 67998

Other (OTH) AF: 0.212 AC: 447 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.48
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs10498769; hg19: chr6-46617318;