rs28669087

chr7-99848351-G-Achr7-99848351-G-Cchr7-99848351-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.521+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,314,736 control chromosomes in the GnomAD database, including 278 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 0.025 (152 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (126 hom.)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A43	NM_057095.3	c.521+97G>A		intron_variant		ENST00000354829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A43	ENST00000354829.7	c.521+97G>A		intron_variant		1	NM_057095.3	A1

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3730 AN: 152116 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00261 AC: 3030 AN: 1162502 Hom.: 126 AF XY: 0.00228 AC XY: 1324 AN XY: 581584

Gnomad4 AFR exome AF: 0.0872

Gnomad4 AMR exome AF: 0.00448

Gnomad4 ASJ exome AF: 0.00511

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000179

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.00565

GnomAD4 genome AF: 0.0246 AC: 3744 AN: 152234 Hom.: 152 Cov.: 32 AF XY: 0.0234 AC XY: 1744 AN XY: 74442

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.00602

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0192 Hom.: 10

Bravo AF: 0.0282

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	5.4
Dann	Benign	0.53

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: rs28669087; hg19: chr7-99445974; COSMIC: COSV55937369;