7-99735184-C-T

Variant names:

• chr7-99735184-C-T
• rs55798860
• NM_000765.5:c.-91G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001256497.3(CYP3A7-CYP3A51P):​c.-91G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,527,170 control chromosomes in the GnomAD database, including 95 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 0.0043 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (87 hom.)
• Consequence: CYP3A7-CYP3A51P NM_001256497.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348
• Publications: 5 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=-0.88).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00431 (656/152256) while in subpopulation SAS AF = 0.0247 (119/4824). AF 95% confidence interval is 0.0211. There are 8 homozygotes in GnomAd4. There are 319 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256497.3. 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.-91G>A		5_prime_UTR	Exon 1 of 13	NP_000756.3
	CYP3A7-CYP3A51P	NM_001256497.3		c.-91G>A		5_prime_UTR	Exon 1 of 15	NP_001243426.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A7	ENST00000336374.4	TSL:1 MANE Select	c.-91G>A		5_prime_UTR	Exon 1 of 13	ENSP00000337450.2
	CYP3A7	ENST00000467776.1	TSL:3	n.13G>A		non_coding_transcript_exon	Exon 1 of 2
	CYP3A7-CYP3A51P	ENST00000620220.6	TSL:1	c.-91G>A		upstream_gene	N/A	ENSP00000479282.3

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 657 AN: 152138 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0249

Gnomad FIN AF: 0.000849

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00649 AC: 8930 AN: 1374914 Hom.: 87 Cov.: 20 AF XY: 0.00743 AC XY: 5101 AN XY: 686552

African (AFR) AF: 0.00104 AC: 33 AN: 31676

American (AMR) AF: 0.00264 AC: 109 AN: 41284

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 293 AN: 25270

East Asian (EAS) AF: 0.000131 AC: 5 AN: 38230

South Asian (SAS) AF: 0.0303 AC: 2525 AN: 83284

European-Finnish (FIN) AF: 0.000757 AC: 39 AN: 51498

Middle Eastern (MID) AF: 0.0262 AC: 146 AN: 5574

European-Non Finnish (NFE) AF: 0.00520 AC: 5413 AN: 1040622

Other (OTH) AF: 0.00639 AC: 367 AN: 57476

GnomAD4 genome AF: 0.00431 AC: 656 AN: 152256 Hom.: 8 Cov.: 31 AF XY: 0.00429 AC XY: 319 AN XY: 74428

African (AFR) AF: 0.000915 AC: 38 AN: 41546

American (AMR) AF: 0.00346 AC: 53 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4824

European-Finnish (FIN) AF: 0.000849 AC: 9 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00560 AC: 381 AN: 68016

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00522 Hom.: 3

Bravo AF: 0.00365

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.35
PromoterAI		-0.0081	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55798860; hg19: chr7-99332807;