rs2687075

Variant names:

• chr7-99717363-A-G
• rs2687075
• NM_000765.5:c.433-98T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-99717363-A-G
• chr7-99717363-A-T

Variant summary

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

The NM_000765.5(CYP3A7):​c.433-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.869 in 1,603,298 control chromosomes in the GnomAD database, including 615,846 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 (47136 hom., cov: 33)
  • Exomes 𝑓: 0.88 (568710 hom.)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 9 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=-0.89).
• 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 rank	MANE	Protein	UniProt
CYP3A7	NM_000765.5	c.433-98T>C		intron_variant	Intron 5 of 12	ENST00000336374.4	NP_000756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374.4	c.433-98T>C		intron_variant	Intron 5 of 12	1	NM_000765.5	ENSP00000337450.2
CYP3A7-CYP3A51P	ENST00000620220.6	c.433-98T>C		intron_variant	Intron 5 of 12	1		ENSP00000479282.3

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115869 AN: 152074 Hom.: 47122 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: 0.718

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

GnomAD4 exome AF: 0.880 AC: 1276936 AN: 1451106 Hom.: 568710 Cov.: 30 AF XY: 0.877 AC XY: 633368 AN XY: 722576

African (AFR) AF: 0.443 AC: 14700 AN: 33208

American (AMR) AF: 0.774 AC: 34404 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 23581 AN: 26046

East Asian (EAS) AF: 0.738 AC: 29179 AN: 39516

South Asian (SAS) AF: 0.694 AC: 59667 AN: 85924

European-Finnish (FIN) AF: 0.925 AC: 49349 AN: 53342

Middle Eastern (MID) AF: 0.844 AC: 4840 AN: 5732

European-Non Finnish (NFE) AF: 0.916 AC: 1010067 AN: 1102850

Other (OTH) AF: 0.852 AC: 51149 AN: 60014

GnomAD4 genome AF: 0.762 AC: 115924 AN: 152192 Hom.: 47136 Cov.: 33 AF XY: 0.762 AC XY: 56723 AN XY: 74416

African (AFR) AF: 0.460 AC: 19096 AN: 41476

American (AMR) AF: 0.785 AC: 11993 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3128 AN: 3472

East Asian (EAS) AF: 0.718 AC: 3715 AN: 5172

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4824

European-Finnish (FIN) AF: 0.932 AC: 9898 AN: 10618

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

European-Non Finnish (NFE) AF: 0.913 AC: 62098 AN: 68022

Other (OTH) AF: 0.783 AC: 1657 AN: 2116

Alfa AF: 0.869 Hom.: 92291

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	-0.89
CADD	Benign	7.3
DANN	Benign	0.59
PhyloP100		-0.14
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: rs2687075; hg19: chr7-99314986;