rs6960775

Positions:

• chr7-99849797-C-G

Variant summary

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

The NM_057095.3(CYP3A43):​c.670+103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0881 in 1,154,026 control chromosomes in the GnomAD database, including 10,851 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 0.19 (5790 hom., cov: 31)
  • Exomes 𝑓: 0.072 (5061 hom.)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.670+103C>G		intron_variant		ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.670+103C>G		intron_variant		1	NM_057095.3	ENSP00000346887	A1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29407 AN: 151708 Hom.: 5769 Cov.: 31

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.0720 AC: 72182 AN: 1002200 Hom.: 5061 Cov.: 13 AF XY: 0.0715 AC XY: 35644 AN XY: 498864

Gnomad4 AFR exome AF: 0.513

Gnomad4 AMR exome AF: 0.0900

Gnomad4 ASJ exome AF: 0.0882

Gnomad4 EAS exome AF: 0.000415

Gnomad4 SAS exome AF: 0.0682

Gnomad4 FIN exome AF: 0.0582

Gnomad4 NFE exome AF: 0.0622

Gnomad4 OTH exome AF: 0.0890

GnomAD4 genome AF: 0.194 AC: 29477 AN: 151826 Hom.: 5790 Cov.: 31 AF XY: 0.189 AC XY: 14022 AN XY: 74216

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0737

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.169

Alfa AF: 0.146 Hom.: 438

Bravo AF: 0.213

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.60

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: rs6960775; hg19: chr7-99447420;