rs517284

Positions:

• chr7-99857132-G-A
• chr7-99857132-G-C
• chr7-99857132-G-T

Variant summary

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

The NM_057095.3(CYP3A43):​c.865+233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,046 control chromosomes in the GnomAD database, including 2,749 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 0.14 (2749 hom., cov: 32)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.865+233G>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.865+233G>A		intron_variant		1	NM_057095.3	ENSP00000346887	A1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20573 AN: 151928 Hom.: 2736 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0844

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0553

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.136 AC: 20624 AN: 152046 Hom.: 2749 Cov.: 32 AF XY: 0.133 AC XY: 9854 AN XY: 74340

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.0843

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0447

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0553

Gnomad4 OTH AF: 0.118

Alfa AF: 0.0871 Hom.: 225

Bravo AF: 0.145

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.47

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: rs517284; hg19: chr7-99454755;