rs4646453

Positions:

• chr7-99662739-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000777.5(CYP3A5):​c.865+77G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,376,960 control chromosomes in the GnomAD database, including 4,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.060 (549 hom., cov: 32)
  • Exomes 𝑓: 0.047 (4102 hom.)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

CYP3A5 (HGNC:2638): (cytochrome P450 family 3 subfamily A member 5) 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. The encoded protein metabolizes drugs as well as the steroid hormones testosterone and progesterone. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Two pseudogenes of this gene have been identified within this cluster on chromosome 7. Expression of this gene is widely variable among populations, and a single nucleotide polymorphism that affects transcript splicing has been associated with susceptibility to hypertensions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ZSCAN25 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-99662739-C-A is Benign according to our data. Variant chr7-99662739-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.865+77G>T		intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.865+77G>T		intron_variant		1	NM_000777.5	P1

Frequencies

GnomAD3 genomes AF: 0.0596 AC: 9063 AN: 152122 Hom.: 552 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0640

GnomAD4 exome AF: 0.0469 AC: 57388 AN: 1224720 Hom.: 4102 AF XY: 0.0516 AC XY: 31991 AN XY: 620112

Gnomad4 AFR exome AF: 0.0773

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.0318

Gnomad4 EAS exome AF: 0.238

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.0148

Gnomad4 NFE exome AF: 0.0216

Gnomad4 OTH exome AF: 0.0553

GnomAD4 genome AF: 0.0596 AC: 9071 AN: 152240 Hom.: 549 Cov.: 32 AF XY: 0.0653 AC XY: 4859 AN XY: 74430

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0633

Alfa AF: 0.0439 Hom.: 125

Bravo AF: 0.0625

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.58

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: rs4646453; hg19: chr7-99260362; COSMIC: COSV56119062; COSMIC: COSV56119062;