rs651430

Positions:

• chr7-99832220-A-G
• chr7-99832220-A-T

Variant summary

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

The NM_057095.3(CYP3A43):​c.71+4034A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,394 control chromosomes in the GnomAD database, including 26,385 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 (26385 hom., cov: 27)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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=-0.91).
• 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	UniProt
CYP3A43	NM_057095.3	c.71+4034A>G		intron_variant		ENST00000354829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A43	ENST00000354829.7	c.71+4034A>G		intron_variant		1	NM_057095.3	A1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85530 AN: 151276 Hom.: 26336 Cov.: 27

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.525

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.566 AC: 85634 AN: 151394 Hom.: 26385 Cov.: 27 AF XY: 0.562 AC XY: 41521 AN XY: 73936

Gnomad4 AFR AF: 0.831

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.522

Alfa AF: 0.477 Hom.: 30445

Bravo AF: 0.574

Asia WGS AF: 0.481 AC: 1675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs651430; hg19: chr7-99429843;