rs2687144

Positions:

• chr7-99721185-C-T

Variant summary

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

The NM_000765.5(CYP3A7):​c.219-773G>A 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 152,136 control chromosomes in the GnomAD database, including 47,148 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 (47148 hom., cov: 32)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-0.96).
• 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	Protein	UniProt
CYP3A7	NM_000765.5	c.219-773G>A		intron_variant		ENST00000336374.4	NP_000756.3
CYP3A7-CYP3A51P	NM_001256497.3	c.219-773G>A		intron_variant			NP_001243426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374.4	c.219-773G>A		intron_variant		1	NM_000765.5	ENSP00000337450	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115879 AN: 152018 Hom.: 47134 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.782

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

GnomAD4 genome AF: 0.762 AC: 115935 AN: 152136 Hom.: 47148 Cov.: 32 AF XY: 0.763 AC XY: 56728 AN XY: 74390

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.783

Alfa AF: 0.832 Hom.: 6813

Bravo AF: 0.741

Asia WGS AF: 0.672 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.47

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: rs2687144; hg19: chr7-99318808;