6-46603046-C-G

Position:

• chr6-46603046-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.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

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]

CYP39A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP39A1	NM_016593.5	c.932-6926G>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.932-6926G>C		intron_variant		1	NM_016593.5	ENSP00000275016.2
CYP39A1	ENST00000619708.4	c.416-6926G>C		intron_variant		1		ENSP00000477769.1
CYP39A1	ENST00000480804.1	n.243-6926G>C		intron_variant		5
RCAN2-DT	ENST00000657801.1	n.287-2885C>G		intron_variant

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

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.511

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.82

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: rs6458511; hg19: chr6-46570783;