7-99648865-C-T

Position:

• chr7-99648865-C-T

Variant summary

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

The NM_000777.5(CYP3A5):​c.1414-465G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 152,180 control chromosomes in the GnomAD database, including 62 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 0.017 (62 hom., cov: 32)
• Consequence: CYP3A5 NM_000777.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

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 = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A5	NM_000777.5	c.1414-465G>A		intron_variant		ENST00000222982.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A5	ENST00000222982.8	c.1414-465G>A		intron_variant		1	NM_000777.5	P1
CYP3A5	ENST00000646887.1	c.*1099-465G>A		intron_variant, NMD_transcript_variant
CYP3A5	ENST00000461920.5	n.2006-465G>A		intron_variant, non_coding_transcript_variant		2
CYP3A5	ENST00000469887.5	n.2947-465G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 2575 AN: 152062 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0163

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0169 AC: 2576 AN: 152180 Hom.: 62 Cov.: 32 AF XY: 0.0160 AC XY: 1193 AN XY: 74402

Gnomad4 AFR AF: 0.0570

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0115 Hom.: 11

Bravo AF: 0.0199

Asia WGS AF: 0.00202 AC: 8 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	0.25
DANN	Benign	0.61

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: rs28365076; hg19: chr7-99246488;