rs1419745

Variant names:

• chr7-99662469-T-C
• rs1419745
• NM_000777.5:c.865+347A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000777.5(CYP3A5):​c.865+347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,146 control chromosomes in the GnomAD database, including 3,899 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 0.15 (3899 hom., cov: 32)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 11 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000777.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	NM_000777.5	MANE Select	c.865+347A>G		intron	N/A	NP_000768.1
	CYP3A5	NM_001291830.2		c.835+347A>G		intron	N/A	NP_001278759.1
	CYP3A5	NM_001291829.2		c.526+347A>G		intron	N/A	NP_001278758.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	ENST00000222982.8	TSL:1 MANE Select	c.865+347A>G		intron	N/A	ENSP00000222982.4
	CYP3A5	ENST00000463364.5	TSL:1	n.1184+347A>G		intron	N/A
	CYP3A5	ENST00000481825.5	TSL:1	n.2550+347A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23267 AN: 152028 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0242

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.153 AC: 23324 AN: 152146 Hom.: 3899 Cov.: 32 AF XY: 0.155 AC XY: 11561 AN XY: 74384

African (AFR) AF: 0.398 AC: 16494 AN: 41436

American (AMR) AF: 0.134 AC: 2042 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.254 AC: 1315 AN: 5172

South Asian (SAS) AF: 0.255 AC: 1228 AN: 4822

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0242 AC: 1646 AN: 68024

Other (OTH) AF: 0.132 AC: 278 AN: 2108

Alfa AF: 0.0677 Hom.: 1904

Bravo AF: 0.169

Asia WGS AF: 0.269 AC: 936 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-1.4
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: rs1419745; hg19: chr7-99260092;