rs523407

Variant names:

• chr7-99837570-A-T
• rs523407
• NM_057095.3:c.165+1024A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_057095.3(CYP3A43):​c.165+1024A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,098 control chromosomes in the GnomAD database, including 7,116 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 0.21 (7116 hom., cov: 32)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.165+1024A>T		intron_variant	Intron 2 of 12	ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.165+1024A>T		intron_variant	Intron 2 of 12	1	NM_057095.3	ENSP00000346887.3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32041 AN: 151980 Hom.: 7094 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0703

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.211 AC: 32110 AN: 152098 Hom.: 7116 Cov.: 32 AF XY: 0.206 AC XY: 15292 AN XY: 74370

African (AFR) AF: 0.565 AC: 23417 AN: 41418

American (AMR) AF: 0.136 AC: 2074 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0877 AC: 304 AN: 3466

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4828

European-Finnish (FIN) AF: 0.0584 AC: 620 AN: 10614

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0704 AC: 4785 AN: 67996

Other (OTH) AF: 0.183 AC: 386 AN: 2110

Alfa AF: 0.155 Hom.: 532

Bravo AF: 0.233

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.0
DANN	Benign	0.55
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs523407; hg19: chr7-99435193;