rs4646450

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000777.5(CYP3A5):​c.319-1630C>T variant causes a intron 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_000777.5 intron

Scores

2

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: -0.539
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP3A5NM_000777.5 linkuse as main transcriptc.319-1630C>T intron_variant ENST00000222982.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP3A5ENST00000222982.8 linkuse as main transcriptc.319-1630C>T intron_variant 1 NM_000777.5 P1P20815-1

Frequencies

GnomAD3 genomes
AF:
0.375
AC:
57092
AN:
152060
Hom.:
17393
Cov.:
33
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.843
Gnomad4 AMR
AF:
0.318
Gnomad4 ASJ
AF:
0.165
Gnomad4 EAS
AF:
0.285
Gnomad4 SAS
AF:
0.373
Gnomad4 FIN
AF:
0.180
Gnomad4 NFE
AF:
0.158
Gnomad4 OTH
AF:
0.340
Alfa
AF:
0.190
Hom.:
8448
Bravo
AF:
0.404
Asia WGS
AF:
0.411
AC:
1429
AN:
3478

ClinVar

Significance: association
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

appendicular lean mass relative to body height Other:1
association, no assertion criteria providedreference populationHuman Population Biology Research Unit, Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University-X12063 is an endogenous molecule, one of 360 metabolites identified by Metabolon Inc. using ultrahigh performance liquid chromatography and mass spectrometry. X12063 circulating levels were highly significantly associated with skeletal muscle mass, as assessed by appendicular lean mass relative to body height (p=2.85E-42). GWAS demonstrated that X12063 was associated with 7q22.1 genomic region with top p-value 4.987E-50 for SNP rs4646450:G>A. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.46
DANN
Benign
0.48

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4646450; hg19: chr7-99266318; API