Variant 7-99672720-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000777.5(CYP3A5):c.219-41C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 1,611,512 control chromosomes in the GnomAD database, including 253 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 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.017 ( 232 hom. )

Consequence

CYP3A5
NM_000777.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

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]

CYP3A5 links:

ZSCAN25 (HGNC:):

ZSCAN25 links:

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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=-0.96).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0133 (2019/152186) while in subpopulation NFE AF= 0.0189 (1285/68000). AF 95% confidence interval is 0.018. There are 21 homozygotes in gnomad4. There are 977 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2019 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5 linkuse as main transcript	c.219-41C>A		intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8 linkuse as main transcript	c.219-41C>A		intron_variant		1	NM_000777.5	P1	P20815-1

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2024

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00338

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0164

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.0146

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0144

AC:

3567

AN:

247778

Hom.:

AF XY:

0.0149

AC XY:

1991

AN XY:

133746

show subpopulations

Gnomad AFR exome

AF:

0.00346

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.0238

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0101

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0190

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0174

AC:

25349

AN:

1459326

Hom.:

232

Cov.:

AF XY:

0.0172

AC XY:

12501

AN XY:

725812

show subpopulations

Gnomad4 AFR exome

AF:

0.00255

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00936

Gnomad4 FIN exome

AF:

0.0142

Gnomad4 NFE exome

AF:

0.0193

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0133

AC:

2019

AN:

152186

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

977

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00337

Gnomad4 AMR

AF:

0.0164

Gnomad4 ASJ

AF:

0.0271

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00789

Gnomad4 FIN

AF:

0.0146

Gnomad4 NFE

AF:

0.0189

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.0128

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.83

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over