rs2740560

Variant names:

• chr7-99724697-T-A
• rs2740560
• NM_000765.5:c.166-2349A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-99724697-T-A
• chr7-99724697-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000765.5(CYP3A7):​c.166-2349A>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 151,912 control chromosomes in the GnomAD database, including 47,073 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 (47073 hom., cov: 30)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 4 publications found

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:51504): (CYP3A7-CYP3A51P readthrough) This locus represents readthrough transcription between the neighboring CYP3A7 (cytochrome P450, family 3, subfamily A, polypeptide 7) and CYP3A51P (cytochrome P450, family 3, subfamily A, polypeptide 51, pseudogene) genes, which are members of the CYP3A gene cluster on chromosome 7. The downstream pseudogene is not known to be independently transcribed. The readthrough transcript includes CYP3A7 exons 1-13 and exons 2 and 13 of the pseudogene. It encodes a CYP3A isoform with a novel C-terminus. This isoform is only expressed in alleles containing a T nucleotide at the -6 position of a splice acceptor in the pseudogene, which enables correct splicing of the upstream CYP3A7 exons to the pseudogene exons. It should be noted that the reference genome sequence represents the CYP3A7_39256 T->A allele, and thus this haplotype is unlikely to produce the readthrough transcript. [provided by RefSeq, Jan 2015]

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• 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 rank	MANE	Protein	UniProt
CYP3A7	NM_000765.5	c.166-2349A>T		intron_variant	Intron 2 of 12	ENST00000336374.4	NP_000756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374.4	c.166-2349A>T		intron_variant	Intron 2 of 12	1	NM_000765.5	ENSP00000337450.2
CYP3A7-CYP3A51P	ENST00000620220.6	c.166-2349A>T		intron_variant	Intron 2 of 12	1		ENSP00000479282.3
CYP3A7-CYP3A51P	ENST00000611620.4	c.166-2349A>T		intron_variant	Intron 2 of 14	5		ENSP00000480571.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115694 AN: 151792 Hom.: 47058 Cov.: 30

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.785

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.793

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: 115754 AN: 151912 Hom.: 47073 Cov.: 30 AF XY: 0.763 AC XY: 56625 AN XY: 74248

African (AFR) AF: 0.460 AC: 19041 AN: 41350

American (AMR) AF: 0.785 AC: 11978 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3127 AN: 3470

East Asian (EAS) AF: 0.721 AC: 3714 AN: 5152

South Asian (SAS) AF: 0.674 AC: 3237 AN: 4806

European-Finnish (FIN) AF: 0.932 AC: 9870 AN: 10590

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62049 AN: 67970

Other (OTH) AF: 0.783 AC: 1653 AN: 2110

Alfa AF: 0.832 Hom.: 6470

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	-0.92
CADD	Benign	2.2
DANN	Benign	0.27
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2740560; hg19: chr7-99322320;