rs61469810

Variant names:

• chr7-99836454-TA-T
• rs61469810
• NM_057095.3:c.74delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_057095.3(CYP3A43):​c.74delA​(p.Tyr25LeufsTer65) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.047 in 1,612,084 control chromosomes in the GnomAD database, including 3,864 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (1491 hom., cov: 31)
  • Exomes 𝑓: 0.042 (2373 hom.)
• Consequence: CYP3A43 NM_057095.3 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• Publications: 16 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	NM_057095.3	MANE Select	c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 13	NP_476436.1
	CYP3A43	NM_022820.5		c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 13	NP_073731.1
	CYP3A43	NM_057096.4		c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 12	NP_476437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 13	ENSP00000346887.3
	CYP3A43	ENST00000222382.5	TSL:1	c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 13	ENSP00000222382.5
	CYP3A43	ENST00000312017.9	TSL:1	c.74delA	p.Tyr25LeufsTer65	frameshift splice_region	Exon 2 of 12	ENSP00000312110.5

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14969 AN: 152126 Hom.: 1488 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0985

GnomAD2 exomes AF: 0.0505 AC: 12637 AN: 250348 AF XY: 0.0483

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0353

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000273

Gnomad FIN exome AF: 0.0201

Gnomad NFE exome AF: 0.0376

Gnomad OTH exome AF: 0.0454

GnomAD4 exome AF: 0.0416 AC: 60746 AN: 1459840 Hom.: 2373 Cov.: 29 AF XY: 0.0419 AC XY: 30425 AN XY: 726224

African (AFR) AF: 0.271 AC: 9013 AN: 33314

American (AMR) AF: 0.0385 AC: 1714 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.0572 AC: 1491 AN: 26088

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39684

South Asian (SAS) AF: 0.0573 AC: 4922 AN: 85916

European-Finnish (FIN) AF: 0.0194 AC: 1038 AN: 53384

Middle Eastern (MID) AF: 0.0841 AC: 485 AN: 5764

European-Non Finnish (NFE) AF: 0.0351 AC: 38956 AN: 1110792

Other (OTH) AF: 0.0517 AC: 3120 AN: 60322

GnomAD4 genome AF: 0.0985 AC: 15000 AN: 152244 Hom.: 1491 Cov.: 31 AF XY: 0.0970 AC XY: 7222 AN XY: 74454

African (AFR) AF: 0.255 AC: 10596 AN: 41506

American (AMR) AF: 0.0568 AC: 868 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0527 AC: 183 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0593 AC: 286 AN: 4826

European-Finnish (FIN) AF: 0.0219 AC: 233 AN: 10622

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.0377 AC: 2563 AN: 68016

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0302 Hom.: 33

Bravo AF: 0.107

Asia WGS AF: 0.0350 AC: 121 AN: 3478

EpiCase AF: 0.0426

EpiControl AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3
Mutation Taster		=37/163	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs61469810; hg19: chr7-99434077; COSMIC: COSV55937274;