rs6976017

Positions:

• chr7-99652376-G-A
• chr7-99652376-G-T

Variant summary

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

The NM_000777.5(CYP3A5):​c.1253+177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0511 in 498,110 control chromosomes in the GnomAD database, including 951 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 0.068 (488 hom., cov: 32)
  • Exomes 𝑓: 0.044 (463 hom.)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A5	NM_000777.5	c.1253+177C>T		intron_variant		ENST00000222982.8	NP_000768.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A5	ENST00000222982.8	c.1253+177C>T		intron_variant		1	NM_000777.5	ENSP00000222982	P1

Frequencies

GnomAD3 genomes AF: 0.0676 AC: 10268 AN: 151884 Hom.: 490 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.0262

Gnomad SAS AF: 0.0448

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0434

Gnomad OTH AF: 0.0558

GnomAD4 exome AF: 0.0438 AC: 15171 AN: 346106 Hom.: 463 Cov.: 4 AF XY: 0.0430 AC XY: 7699 AN XY: 179208

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.0360

Gnomad4 EAS exome AF: 0.0191

Gnomad4 SAS exome AF: 0.0358

Gnomad4 FIN exome AF: 0.0538

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.0478

GnomAD4 genome AF: 0.0676 AC: 10275 AN: 152004 Hom.: 488 Cov.: 32 AF XY: 0.0658 AC XY: 4887 AN XY: 74308

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.0263

Gnomad4 SAS AF: 0.0454

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0434

Gnomad4 OTH AF: 0.0552

Alfa AF: 0.0257 Hom.: 12

Bravo AF: 0.0718

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.042
DANN	Benign	0.69

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: rs6976017; hg19: chr7-99249999;