rs2037498

Positions:

• chr7-99713927-G-A
• chr7-99713927-G-C

Variant summary

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

The NM_000765.5(CYP3A7):​c.799-392C>T 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 152,050 control chromosomes in the GnomAD database, including 47,098 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 (47098 hom., cov: 31)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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=-0.89).
• 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.799-392C>T		intron_variant		ENST00000336374.4
CYP3A7-CYP3A51P	NM_001256497.3	c.799-392C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A7	ENST00000336374.4	c.799-392C>T		intron_variant		1	NM_000765.5	P1
CYP3A7	ENST00000477357.5	n.1138-392C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115779 AN: 151932 Hom.: 47084 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.673

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: 115835 AN: 152050 Hom.: 47098 Cov.: 31 AF XY: 0.762 AC XY: 56673 AN XY: 74346

Gnomad4 AFR AF: 0.461

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.784

Alfa AF: 0.882 Hom.: 78340

Bravo AF: 0.741

Asia WGS AF: 0.671 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2037498; hg19: chr7-99311550;