rs8175345

Positions:

• chr7-99672695-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000777.5(CYP3A5):​c.219-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,613,420 control chromosomes in the GnomAD database, including 183 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 0.019 (104 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (79 hom.)
• Consequence: CYP3A5 NM_000777.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.219-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.219-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000777.5	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2915 AN: 152108 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00527 AC: 1318 AN: 250146 Hom.: 44 AF XY: 0.00386 AC XY: 522 AN XY: 135148

Gnomad AFR exome AF: 0.0676

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.00588

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.000451

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00225 AC: 3292 AN: 1461194 Hom.: 79 Cov.: 30 AF XY: 0.00194 AC XY: 1413 AN XY: 726846

Gnomad4 AFR exome AF: 0.0662

Gnomad4 AMR exome AF: 0.00343

Gnomad4 ASJ exome AF: 0.00517

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000186

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000426

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.0192 AC: 2924 AN: 152226 Hom.: 104 Cov.: 32 AF XY: 0.0190 AC XY: 1414 AN XY: 74422

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.00713

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00321 Hom.: 19

Bravo AF: 0.0214

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	12
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs8175345; hg19: chr7-99270318;