NM_000765.5:c.319-1161C>A

Variant names:

• chr7-99718800-G-T
• rs2687074
• NM_000765.5:c.319-1161C>A

Variant summary

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

The NM_000765.5(CYP3A7):​c.319-1161C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,302 control chromosomes in the GnomAD database, including 67,965 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 0.94 (67965 hom., cov: 33)
• Consequence: CYP3A7 NM_000765.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632
• Publications: 1 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000765.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A7	NM_000765.5	MANE Select	c.319-1161C>A		intron	N/A	NP_000756.3
	CYP3A7-CYP3A51P	NM_001256497.3		c.319-1161C>A		intron	N/A	NP_001243426.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A7	ENST00000336374.4	TSL:1 MANE Select	c.319-1161C>A		intron	N/A	ENSP00000337450.2
	CYP3A7-CYP3A51P	ENST00000620220.6	TSL:1	c.319-1161C>A		intron	N/A	ENSP00000479282.3
	CYP3A7-CYP3A51P	ENST00000611620.4	TSL:5	c.319-1161C>A		intron	N/A	ENSP00000480571.1

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143177 AN: 152184 Hom.: 67941 Cov.: 33

Gnomad AFR AF: 0.799

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.956

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

GnomAD4 genome AF: 0.941 AC: 143248 AN: 152302 Hom.: 67965 Cov.: 33 AF XY: 0.942 AC XY: 70181 AN XY: 74472

African (AFR) AF: 0.798 AC: 33158 AN: 41530

American (AMR) AF: 0.968 AC: 14820 AN: 15306

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 1.00 AC: 4831 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10626 AN: 10626

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67942 AN: 68032

Other (OTH) AF: 0.956 AC: 2020 AN: 2114

Alfa AF: 0.983 Hom.: 76491

Bravo AF: 0.933

Asia WGS AF: 0.981 AC: 3401 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.17
PhyloP100		-0.63
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: rs2687074; hg19: chr7-99316423;