ENST00000466061.5:n.27C>T

Variant names:

• chr7-99679970-G-A
• rs28371764
• ENST00000466061.5:n.27C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000466061.5(CYP3A5):​n.27C>T variant causes a non coding transcript exon 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 (no stars).

• Frequency:
  • Genomes: 𝑓 0.024 (62 hom., cov: 32)
  • Exomes 𝑓: 0.032 (686 hom.)
• Consequence: CYP3A5 ENST00000466061.5 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0250
• Publications: 14 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 -13 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 VariationId is 3055839.Status of the report is no_assertion_criteria_provided, 0 stars.
• 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 rank	MANE	Protein	UniProt
CYP3A5	NM_000777.5	c.-74C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000222982.8	NP_000768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A5	ENST00000222982.8	c.-74C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_000777.5	ENSP00000222982.4

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

African (AFR) AF: 0.00601 AC: 168 AN: 27966

American (AMR) AF: 0.0191 AC: 845 AN: 44164

Ashkenazi Jewish (ASJ) AF: 0.0436 AC: 1059 AN: 24294

East Asian (EAS) AF: 0.000209 AC: 8 AN: 38308

South Asian (SAS) AF: 0.0440 AC: 3538 AN: 80412

European-Finnish (FIN) AF: 0.0210 AC: 1113 AN: 52968

Middle Eastern (MID) AF: 0.0633 AC: 331 AN: 5232

European-Non Finnish (NFE) AF: 0.0334 AC: 28695 AN: 858952

Other (OTH) AF: 0.0308 AC: 1576 AN: 51218

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

African (AFR) AF: 0.00553 AC: 230 AN: 41572

American (AMR) AF: 0.0286 AC: 437 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5182

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4828

European-Finnish (FIN) AF: 0.0229 AC: 243 AN: 10610

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0333 AC: 2268 AN: 68014

Other (OTH) AF: 0.0322 AC: 68 AN: 2112

Alfa AF: 0.0310 Hom.: 221

Bravo AF: 0.0229

Asia WGS AF: 0.0160 AC: 57 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CYP3A5-related disorder Benign:1

Mar 21, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
PhyloP100		0.025
PromoterAI		-0.46	Neutral
Mutation Taster		=300/0	polymorphism

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

Other links and lift over

dbSNP: rs28371764; hg19: chr7-99277593;