7-99648291-A-G

Variant names:

• chr7-99648291-A-G
• rs15524
• NM_000777.5:c.*14T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000777.5(CYP3A5):​c.*14T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,605,368 control chromosomes in the GnomAD database, including 25,133 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 0.24 (8257 hom., cov: 32)
  • Exomes 𝑓: 0.11 (16876 hom.)
• Consequence: CYP3A5 NM_000777.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.485
• Publications: 100 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	NM_000777.5	MANE Select	c.*14T>C		3_prime_UTR	Exon 13 of 13	NP_000768.1
	CYP3A5	NR_033807.3		n.3227T>C		non_coding_transcript_exon	Exon 13 of 13
	CYP3A5	NM_001291830.2		c.*14T>C		3_prime_UTR	Exon 14 of 14	NP_001278759.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A5	ENST00000222982.8	TSL:1 MANE Select	c.*14T>C		3_prime_UTR	Exon 13 of 13	ENSP00000222982.4
	CYP3A5	ENST00000461920.5	TSL:2	n.2115T>C		non_coding_transcript_exon	Exon 14 of 14
	CYP3A5	ENST00000469887.5	TSL:5	n.3056T>C		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37046 AN: 151992 Hom.: 8240 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.0781

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0763

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.170 AC: 41812 AN: 245494 AF XY: 0.162

Gnomad AFR exome AF: 0.594

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.0695

Gnomad EAS exome AF: 0.285

Gnomad FIN exome AF: 0.0710

Gnomad NFE exome AF: 0.0754

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.112 AC: 163207 AN: 1453258 Hom.: 16876 Cov.: 32 AF XY: 0.114 AC XY: 82560 AN XY: 722252

African (AFR) AF: 0.609 AC: 20215 AN: 33184

American (AMR) AF: 0.220 AC: 9536 AN: 43354

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1813 AN: 25834

East Asian (EAS) AF: 0.281 AC: 11125 AN: 39552

South Asian (SAS) AF: 0.274 AC: 23059 AN: 84254

European-Finnish (FIN) AF: 0.0737 AC: 3924 AN: 53214

Middle Eastern (MID) AF: 0.0797 AC: 457 AN: 5736

European-Non Finnish (NFE) AF: 0.0764 AC: 84636 AN: 1108124

Other (OTH) AF: 0.141 AC: 8442 AN: 60006

GnomAD4 genome AF: 0.244 AC: 37113 AN: 152110 Hom.: 8257 Cov.: 32 AF XY: 0.243 AC XY: 18094 AN XY: 74382

African (AFR) AF: 0.585 AC: 24249 AN: 41458

American (AMR) AF: 0.207 AC: 3162 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0781 AC: 271 AN: 3468

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5174

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4816

European-Finnish (FIN) AF: 0.0690 AC: 732 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0763 AC: 5188 AN: 67992

Other (OTH) AF: 0.205 AC: 433 AN: 2108

Alfa AF: 0.125 Hom.: 11345

Bravo AF: 0.266

Asia WGS AF: 0.329 AC: 1142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.81
DANN	Benign	0.67
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs15524; hg19: chr7-99245914; COSMIC: COSV56118640; COSMIC: COSV56118640;