rs800672

Positions:

• chr7-99838575-G-A

Variant summary

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

The ENST00000354829.7(CYP3A43):​c.166-545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 926,220 control chromosomes in the GnomAD database, including 113,299 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 0.57 (26514 hom., cov: 32)
  • Exomes 𝑓: 0.47 (86785 hom.)
• Consequence: CYP3A43 ENST00000354829.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

CYP3A43 (HGNC:17450): (cytochrome P450 family 3 subfamily A member 43) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein has a low level of testosterone hydroxylase activity, and may play a role in aging mechanisms and cancer progression. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.166-545G>A		intron_variant		ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.166-545G>A		intron_variant		1	NM_057095.3	ENSP00000346887	A1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85916 AN: 151862 Hom.: 26465 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.469 AC: 363438 AN: 774240 Hom.: 86785 AF XY: 0.467 AC XY: 181007 AN XY: 387278

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.423

Gnomad4 ASJ exome AF: 0.493

Gnomad4 EAS exome AF: 0.340

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.482

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.477

GnomAD4 genome AF: 0.566 AC: 86020 AN: 151980 Hom.: 26514 Cov.: 32 AF XY: 0.562 AC XY: 41800 AN XY: 74316

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.349

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.523

Alfa AF: 0.484 Hom.: 24517

Bravo AF: 0.574

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs800672; hg19: chr7-99436198;