rs4646446

chr7-99677460-C-T

Variant summary

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

The NM_000777.5(CYP3A5):c.72-1252G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,272 control chromosomes in the GnomAD database, including 529 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 0.058 (529 hom., cov: 32)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.72-1252G>A		intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.72-1252G>A		intron_variant		1	NM_000777.5	P1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8814 AN: 152152 Hom.: 532 Cov.: 32

Gnomad AFR AF: 0.0722

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0904

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0579 AC: 8817 AN: 152272 Hom.: 529 Cov.: 32 AF XY: 0.0638 AC XY: 4749 AN XY: 74442

Gnomad4 AFR AF: 0.0722

Gnomad4 AMR AF: 0.0906

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0328 Hom.: 227

Bravo AF: 0.0606

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	-0.83
Cadd	Benign	0.67
Dann	Benign	0.56

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: rs4646446; hg19: chr7-99275083;