rs10249369

Positions:

• chr7-99649369-A-G

Variant summary

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

The NM_000777.5(CYP3A5):​c.1413+704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 152,298 control chromosomes in the GnomAD database, including 342 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 0.045 (342 hom., cov: 32)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

CYP3A5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A5	NM_000777.5	c.1413+704T>C		intron_variant		ENST00000222982.8	NP_000768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A5	ENST00000222982.8	c.1413+704T>C		intron_variant		1	NM_000777.5	ENSP00000222982.4
CYP3A5	ENST00000461920.5	n.2005+704T>C		intron_variant		2
CYP3A5	ENST00000469887.5	n.2946+704T>C		intron_variant		5
CYP3A5	ENST00000646887.1	n.*1098+704T>C		intron_variant				ENSP00000496704.1

Frequencies

GnomAD3 genomes AF: 0.0446 AC: 6790 AN: 152180 Hom.: 335 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00995

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0448 AC: 6824 AN: 152298 Hom.: 342 Cov.: 32 AF XY: 0.0444 AC XY: 3310 AN XY: 74476

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.00995

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0165 Hom.: 46

Bravo AF: 0.0472

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.34
DANN	Benign	0.54

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: rs10249369; hg19: chr7-99246992;