rs1357319

Positions:

• chr7-99712558-A-C
• chr7-99712558-A-G

Variant summary

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

The NM_000765.5(CYP3A7):​c.865+911T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,156 control chromosomes in the GnomAD database, including 47,135 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 0.76 (47135 hom., cov: 33)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747

Genes affected

CYP3A7 (HGNC:2640): (cytochrome P450 family 3 subfamily A member 7) This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the synthesis of cholesterol, steroids and other lipids. This enzyme hydroxylates testosterone and dehydroepiandrosterone 3-sulphate, which is involved in the formation of estriol during pregnancy. This gene is part of a cluster of related genes on chromosome 7q21.1. Naturally-occurring readthrough transcription occurs between this gene and the downstream CYP3A51P pseudogene and is represented by GeneID:100861540. [provided by RefSeq, Jan 2015]

CYP3A7-CYP3A51P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A7	NM_000765.5	c.865+911T>G		intron_variant		ENST00000336374.4
CYP3A7-CYP3A51P	NM_001256497.3	c.865+911T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A7	ENST00000336374.4	c.865+911T>G		intron_variant		1	NM_000765.5	P1
CYP3A7	ENST00000477357.5	n.1204+911T>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115862 AN: 152038 Hom.: 47121 Cov.: 33

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.762 AC: 115916 AN: 152156 Hom.: 47135 Cov.: 33 AF XY: 0.762 AC XY: 56730 AN XY: 74406

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.784

Alfa AF: 0.874 Hom.: 68228

Bravo AF: 0.741

Asia WGS AF: 0.671 AC: 2335 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.75

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: rs1357319; hg19: chr7-99310181;