6-46603046-C-G

Variant names:

• chr6-46603046-C-G
• rs6458511
• NM_016593.5:c.932-6926G>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.932-6926G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,938 control chromosomes in the GnomAD database, including 25,113 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 0.53 (25113 hom., cov: 31)
• Consequence: CYP39A1 NM_016593.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 4 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]

RCAN2-DT (HGNC:55661): (RCAN2 divergent transcript)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 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.932-6926G>C		intron	N/A	NP_057677.2
	CYP39A1	NM_001278738.2		c.872-6926G>C		intron	N/A	NP_001265667.1
	CYP39A1	NM_001278739.2		c.416-6926G>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.932-6926G>C		intron	N/A	ENSP00000275016.2	Q9NYL5
	CYP39A1	ENST00000619708.4	TSL:1	c.416-6926G>C		intron	N/A	ENSP00000477769.1	A0A087WTD2
	CYP39A1	ENST00000889608.1		c.932-6926G>C		intron	N/A	ENSP00000559667.1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79973 AN: 151820 Hom.: 25057 Cov.: 31

Gnomad AFR AF: 0.872

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.527 AC: 80086 AN: 151938 Hom.: 25113 Cov.: 31 AF XY: 0.531 AC XY: 39389 AN XY: 74228

African (AFR) AF: 0.872 AC: 36183 AN: 41476

American (AMR) AF: 0.519 AC: 7923 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1577 AN: 3462

East Asian (EAS) AF: 0.532 AC: 2727 AN: 5128

South Asian (SAS) AF: 0.672 AC: 3238 AN: 4816

European-Finnish (FIN) AF: 0.358 AC: 3776 AN: 10546

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23122 AN: 67942

Other (OTH) AF: 0.511 AC: 1080 AN: 2112

Alfa AF: 0.282 Hom.: 752

Bravo AF: 0.548

Asia WGS AF: 0.630 AC: 2193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		-0.18
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: rs6458511; hg19: chr6-46570783;