rs55798860

Positions:

• chr7-99735184-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000765.5(CYP3A7):​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. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0043 (8 hom., cov: 31)
  • Exomes 𝑓: 0.0065 (87 hom.)
• Consequence: CYP3A7 NM_000765.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

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]

CYP3A7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 7-99735184-C-T is Benign according to our data. Variant chr7-99735184-C-T is described in Lovd as [Likely_benign].
• 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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A7	NM_000765.5	c.-91G>A		5_prime_UTR_variant	1/13	ENST00000336374.4	NP_000756.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374.4	c.-91G>A		5_prime_UTR_variant	1/13	1	NM_000765.5	ENSP00000337450.2
CYP3A7	ENST00000467776.1	n.13G>A		non_coding_transcript_exon_variant	1/2	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

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.0116

Gnomad4 EAS exome AF: 0.000131

Gnomad4 SAS exome AF: 0.0303

Gnomad4 FIN exome AF: 0.000757

Gnomad4 NFE exome AF: 0.00520

Gnomad4 OTH exome AF: 0.00639

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

Gnomad4 AFR AF: 0.000915

Gnomad4 AMR AF: 0.00346

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.000849

Gnomad4 NFE AF: 0.00560

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00547 Hom.: 1

Bravo AF: 0.00365

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55798860; hg19: chr7-99332807;