rs4646450

Variant names:

• chr7-99668695-G-A
• rs4646450
• NM_000777.5:c.319-1630C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-99668695-G-A
• chr7-99668695-G-C
• chr7-99668695-G-T

Variant summary

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

The NM_001190484.3(CYP3A5):​c.*3079C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,178 control chromosomes in the GnomAD database, including 17,458 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.38 (17458 hom., cov: 33)
• Consequence: CYP3A5 NM_001190484.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.539
• Publications: 53 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190484.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	NM_000777.5	MANE Select	c.319-1630C>T		intron	N/A	NP_000768.1
	CYP3A5	NM_001190484.3		c.*3079C>T		3_prime_UTR	Exon 5 of 5	NP_001177413.1
	CYP3A5	NM_001291830.2		c.289-1630C>T		intron	N/A	NP_001278759.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	ENST00000222982.8	TSL:1 MANE Select	c.319-1630C>T		intron	N/A	ENSP00000222982.4
	CYP3A5	ENST00000463364.5	TSL:1	n.629-1630C>T		intron	N/A
	CYP3A5	ENST00000466061.5	TSL:1	n.659-1630C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57092 AN: 152060 Hom.: 17393 Cov.: 33

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.376 AC: 57223 AN: 152178 Hom.: 17458 Cov.: 33 AF XY: 0.376 AC XY: 27962 AN XY: 74402

African (AFR) AF: 0.843 AC: 34970 AN: 41504

American (AMR) AF: 0.318 AC: 4871 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.285 AC: 1477 AN: 5178

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4820

European-Finnish (FIN) AF: 0.180 AC: 1908 AN: 10594

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10740 AN: 67998

Other (OTH) AF: 0.340 AC: 719 AN: 2114

Alfa AF: 0.217 Hom.: 18199

Bravo AF: 0.404

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	appendicular lean mass relative to body height (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.48
PhyloP100		-0.54
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: rs4646450; hg19: chr7-99266318;