chr7-99735184-C-T

Position:

• 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:):

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	UniProt
CYP3A7	NM_000765.5	c.-91G>A		5_prime_UTR_variant	1/13	ENST00000336374.4
CYP3A7-CYP3A51P	NM_001256497.3	c.-91G>A		5_prime_UTR_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A7	ENST00000336374.4	c.-91G>A		5_prime_UTR_variant	1/13	1	NM_000765.5	P1
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;