rs17161983

Variant names:

• chr7-99866195-A-G
• rs17161983
• NM_057095.3:c.*194A>G

Variant summary

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

The NM_057095.3(CYP3A43):​c.*194A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 345,052 control chromosomes in the GnomAD database, including 1,236 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 0.066 (1029 hom., cov: 32)
  • Exomes 𝑓: 0.014 (207 hom.)
• Consequence: CYP3A43 NM_057095.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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 = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.*194A>G		downstream_gene_variant		ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.*194A>G		downstream_gene_variant		1	NM_057095.3	ENSP00000346887.3

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10024 AN: 152100 Hom.: 1028 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0343

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00234

Gnomad OTH AF: 0.0580

GnomAD4 exome AF: 0.0136 AC: 2617 AN: 192834 Hom.: 207 AF XY: 0.0124 AC XY: 1232 AN XY: 98974

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.0524

Gnomad4 ASJ exome AF: 0.00402

Gnomad4 EAS exome AF: 0.000352

Gnomad4 SAS exome AF: 0.00998

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00272

Gnomad4 OTH exome AF: 0.0299

GnomAD4 genome AF: 0.0660 AC: 10051 AN: 152218 Hom.: 1029 Cov.: 32 AF XY: 0.0638 AC XY: 4749 AN XY: 74446

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.0343

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.000770

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00234

Gnomad4 OTH AF: 0.0588

Alfa AF: 0.0130 Hom.: 229

Bravo AF: 0.0775

Asia WGS AF: 0.0270 AC: 94 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	0.044
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17161983; hg19: chr7-99463818;