rs28371764

chr7-99679970-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000777.5(CYP3A5):c.-74C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0307 in 1,335,804 control chromosomes in the GnomAD database, including 748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.032 (686 hom.)
• Consequence: CYP3A5 NM_000777.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0250

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-99679970-G-A is Benign according to our data. Variant chr7-99679970-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055839.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-99679970-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.-74C>T		5_prime_UTR_variant	1/13	ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.-74C>T		5_prime_UTR_variant	1/13	1	NM_000777.5	P1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 3649 AN: 152172 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0333

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0315 AC: 37333 AN: 1183514 Hom.: 686 Cov.: 16 AF XY: 0.0326 AC XY: 19616 AN XY: 601746

Gnomad4 AFR exome AF: 0.00601

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0436

Gnomad4 EAS exome AF: 0.000209

Gnomad4 SAS exome AF: 0.0440

Gnomad4 FIN exome AF: 0.0210

Gnomad4 NFE exome AF: 0.0334

Gnomad4 OTH exome AF: 0.0308

GnomAD4 genome AF: 0.0240 AC: 3651 AN: 152290 Hom.: 62 Cov.: 32 AF XY: 0.0242 AC XY: 1804 AN XY: 74458

Gnomad4 AFR AF: 0.00553

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0333

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.0336 Hom.: 160

Bravo AF: 0.0229

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CYP3A5-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.1
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28371764; hg19: chr7-99277593;