chr7-99705371-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 NM_000765.5(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 NM_000765.5 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: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 -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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A7	ENST00000336374	c.*129A>G		3_prime_UTR_variant	13/13	1	NM_000765.5	ENSP00000337450.2
CYP3A7-CYP3A51P	ENST00000620220.6	c.1416+2441A>G		intron_variant		1		ENSP00000479282.3
CYP3A7-CYP3A51P	ENST00000611620.4	c.1497+144A>G		intron_variant		5		ENSP00000480571.1
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;