7-99659221-A-G

Position:

• chr7-99659221-A-G

Variant summary

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

The NM_000777.5(CYP3A5):​c.1026+1278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 151,880 control chromosomes in the GnomAD database, including 8,133 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 (8133 hom., cov: 32)
  • Exomes 𝑓: 0.091 (0 hom.)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.1026+1278T>C		intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.1026+1278T>C		intron_variant		1	NM_000777.5	P1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36280 AN: 151740 Hom.: 8115 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0776

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0681

Gnomad OTH AF: 0.204

GnomAD4 exome AF: 0.0909 AC: 2 AN: 22 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 2 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.239 AC: 36348 AN: 151858 Hom.: 8133 Cov.: 32 AF XY: 0.239 AC XY: 17736 AN XY: 74228

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0776

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.0681

Gnomad4 OTH AF: 0.202

Alfa AF: 0.149 Hom.: 510

Bravo AF: 0.261

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.37

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: rs7780328; hg19: chr7-99256844;