7-99705371-T-C

Position:

• chr7-99705371-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336374.4(CYP3A7):​c.*129A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,072,418 control chromosomes in the GnomAD database, including 21,885 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 0.25 (8401 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13484 hom.)
• Consequence: CYP3A7 ENST00000336374.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A7	NM_000765.5	c.*129A>G		3_prime_UTR_variant	13/13	ENST00000336374.4	NP_000756.3
CYP3A7-CYP3A51P	NM_001256497.3	c.1497+144A>G		intron_variant			NP_001243426.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374.4	c.*129A>G		3_prime_UTR_variant	13/13	1	NM_000765.5	ENSP00000337450	P1
CYP3A7	ENST00000477357.5	n.1980A>G		non_coding_transcript_exon_variant	10/10	2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38102 AN: 151950 Hom.: 8380 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.0991

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.0679

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.131 AC: 120830 AN: 920350 Hom.: 13484 Cov.: 12 AF XY: 0.135 AC XY: 64417 AN XY: 475570

Gnomad4 AFR exome AF: 0.604

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.0958

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.0740

Gnomad4 NFE exome AF: 0.0852

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.251 AC: 38170 AN: 152068 Hom.: 8401 Cov.: 32 AF XY: 0.250 AC XY: 18604 AN XY: 74364

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.0991

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.0679

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.227

Alfa AF: 0.112 Hom.: 3154

Bravo AF: 0.274

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10211; hg19: chr7-99302994;