7-99679982-C-T

Variant names:

• chr7-99679982-C-T
• rs28365095
• NM_000777.5:c.-86G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000777.5(CYP3A5):​c.-86G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,181,650 control chromosomes in the GnomAD database, including 119 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 0.0094 (19 hom., cov: 32)
  • Exomes 𝑓: 0.012 (100 hom.)
• Consequence: CYP3A5 NM_000777.5 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0750
• Publications: 5 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-99679982-C-T is Benign according to our data. Variant chr7-99679982-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3041648.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 1434 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000777.5. 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.-86G>A		5_prime_UTR	Exon 1 of 13	NP_000768.1	P20815-1
	CYP3A5	NM_001291830.2		c.-376G>A		5_prime_UTR	Exon 1 of 14	NP_001278759.1
	CYP3A5	NM_001291829.2		c.-925G>A		5_prime_UTR	Exon 1 of 14	NP_001278758.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	ENST00000222982.8	TSL:1 MANE Select	c.-86G>A		5_prime_UTR	Exon 1 of 13	ENSP00000222982.4	P20815-1
	CYP3A5	ENST00000466061.5	TSL:1	n.15G>A		non_coding_transcript_exon	Exon 1 of 10
	CYP3A5	ENST00000481825.5	TSL:1	n.15G>A		non_coding_transcript_exon	Exon 1 of 11

Frequencies

GnomAD3 genomes AF: 0.00942 AC: 1433 AN: 152162 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00217

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00576

GnomAD4 exome AF: 0.0119 AC: 12271 AN: 1029370 Hom.: 100 Cov.: 14 AF XY: 0.0116 AC XY: 6161 AN XY: 530460

African (AFR) AF: 0.00203 AC: 51 AN: 25076

American (AMR) AF: 0.00261 AC: 114 AN: 43662

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 67 AN: 23240

East Asian (EAS) AF: 0.00 AC: 0 AN: 37556

South Asian (SAS) AF: 0.00113 AC: 87 AN: 76812

European-Finnish (FIN) AF: 0.0319 AC: 1679 AN: 52588

Middle Eastern (MID) AF: 0.00101 AC: 5 AN: 4954

European-Non Finnish (NFE) AF: 0.0137 AC: 9872 AN: 719340

Other (OTH) AF: 0.00858 AC: 396 AN: 46142

GnomAD4 genome AF: 0.00942 AC: 1434 AN: 152280 Hom.: 19 Cov.: 32 AF XY: 0.0100 AC XY: 748 AN XY: 74458

African (AFR) AF: 0.00217 AC: 90 AN: 41560

American (AMR) AF: 0.00555 AC: 85 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 879 AN: 68012

Other (OTH) AF: 0.00570 AC: 12 AN: 2104

Alfa AF: 0.00665 Hom.: 0

Bravo AF: 0.00656

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CYP3A5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.4
DANN	Benign	0.81
PhyloP100		-0.075
PromoterAI		-0.053	Neutral
Mutation Taster		=300/0	polymorphism

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: rs28365095; hg19: chr7-99277605; COSMIC: COSV56122594; COSMIC: COSV56122594;