rs2257401

chr7-99709062-G-C

Variant summary

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

The NM_000765.5(CYP3A7):c.1226C>G(p.Thr409Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,714 control chromosomes in the GnomAD database, including 24,610 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.24 (7206 hom., cov: 32)
  • Exomes 𝑓: 0.12 (17404 hom.)
• Consequence: CYP3A7 NM_000765.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.42

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 (MetaRNN=0.0073284805).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A7	NM_000765.5	c.1226C>G	p.Thr409Arg	missense_variant	11/13	ENST00000336374.4
CYP3A7-CYP3A51P	NM_001256497.3	c.1226C>G	p.Thr409Arg	missense_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A7	ENST00000336374.4	c.1226C>G	p.Thr409Arg	missense_variant	11/13	1	NM_000765.5	P1
CYP3A7	ENST00000477357.5	n.1565C>G		non_coding_transcript_exon_variant	8/10	2

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35953 AN: 151910 Hom.: 7189 Cov.: 32

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0990

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.0678

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.120 AC: 175418 AN: 1461686 Hom.: 17404 Cov.: 33 AF XY: 0.123 AC XY: 89734 AN XY: 727144

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.0948

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.0752

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.237 AC: 36015 AN: 152028 Hom.: 7206 Cov.: 32 AF XY: 0.236 AC XY: 17562 AN XY: 74318

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0990

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.0678

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.216

Alfa AF: 0.126 Hom.: 728

Bravo AF: 0.258

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_noAF	Benign	-0.57
Cadd	Benign	20
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0073	T;T;T
Sift4G	Uncertain	0.011	D;D;D
Vest4		0.31
gMVP		0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2257401; hg19: chr7-99306685;