rs585071

Variant names:

• chr7-99829179-A-G
• rs585071
• NM_057095.3:c.71+993A>G

Variant summary

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

The NM_057095.3(CYP3A43):​c.71+993A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,184 control chromosomes in the GnomAD database, including 9,857 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 0.24 (9857 hom., cov: 32)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 6 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]

ENSG00000308518 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057095.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	NM_057095.3	MANE Select	c.71+993A>G		intron	N/A	NP_476436.1	Q9HB55-1
	CYP3A43	NM_022820.5		c.71+993A>G		intron	N/A	NP_073731.1	Q9HB55-2
	CYP3A43	NM_057096.4		c.71+993A>G		intron	N/A	NP_476437.1	Q9HB55-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.71+993A>G		intron	N/A	ENSP00000346887.3	Q9HB55-1
	CYP3A43	ENST00000222382.5	TSL:1	c.71+993A>G		intron	N/A	ENSP00000222382.5	Q9HB55-2
	CYP3A43	ENST00000312017.9	TSL:1	c.71+993A>G		intron	N/A	ENSP00000312110.5	Q9HB55-3

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36538 AN: 152064 Hom.: 9823 Cov.: 32

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0582

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.241 AC: 36629 AN: 152184 Hom.: 9857 Cov.: 32 AF XY: 0.234 AC XY: 17404 AN XY: 74418

African (AFR) AF: 0.669 AC: 27734 AN: 41456

American (AMR) AF: 0.145 AC: 2226 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.00250 AC: 13 AN: 5190

South Asian (SAS) AF: 0.0777 AC: 375 AN: 4824

European-Finnish (FIN) AF: 0.0582 AC: 618 AN: 10614

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0700 AC: 4763 AN: 68012

Other (OTH) AF: 0.205 AC: 433 AN: 2114

Alfa AF: 0.116 Hom.: 4459

Bravo AF: 0.266

Asia WGS AF: 0.0770 AC: 268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.97
DANN	Benign	0.48
PhyloP100		-0.79
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: rs585071; hg19: chr7-99426802;