rs28451617

chr7-99735142-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_000765.5(CYP3A7):c.-49G>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 0.00651 in 1,610,904 control chromosomes in the GnomAD database, including 476 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 0.032 (239 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (237 hom.)
• Consequence: CYP3A7 NM_000765.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458

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=-0.95).
• BP6: Variant 7-99735142-C-T is Benign according to our data. Variant chr7-99735142-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A7	NM_000765.5	c.-49G>A		5_prime_UTR_variant	1/13	ENST00000336374.4
CYP3A7-CYP3A51P	NM_001256497.3	c.-49G>A		5_prime_UTR_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A7	ENST00000336374.4	c.-49G>A		5_prime_UTR_variant	1/13	1	NM_000765.5	P1
CYP3A7	ENST00000467776.1	n.55G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4766 AN: 152088 Hom.: 231 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0224

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.00924 AC: 2299 AN: 248752 Hom.: 99 AF XY: 0.00671 AC XY: 903 AN XY: 134548

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000444

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000866

Gnomad OTH exome AF: 0.00857

GnomAD4 exome AF: 0.00390 AC: 5683 AN: 1458696 Hom.: 237 Cov.: 30 AF XY: 0.00344 AC XY: 2498 AN XY: 725640

Gnomad4 AFR exome AF: 0.111

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000329

Gnomad4 SAS exome AF: 0.000360

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.000691

Gnomad4 OTH exome AF: 0.00850

GnomAD4 genome AF: 0.0315 AC: 4797 AN: 152208 Hom.: 239 Cov.: 31 AF XY: 0.0304 AC XY: 2265 AN XY: 74414

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0224

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0260

Alfa AF: 0.00591 Hom.: 57

Bravo AF: 0.0357

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	3.2
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28451617; hg19: chr7-99332765; COSMIC: COSV60480897;