rs800672

Variant names:

• chr7-99838575-G-A
• rs800672
• NM_057095.3:c.166-545G>A

Variant summary

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

The ENST00000354829.7(CYP3A43):​c.166-545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 926,220 control chromosomes in the GnomAD database, including 113,299 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 0.57 (26514 hom., cov: 32)
  • Exomes 𝑓: 0.47 (86785 hom.)
• Consequence: CYP3A43 ENST00000354829.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 9 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 -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 = 0.824 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000354829.7. 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.166-545G>A		intron	N/A	NP_476436.1
	CYP3A43	NM_022820.5		c.166-545G>A		intron	N/A	NP_073731.1
	CYP3A43	NM_057096.4		c.166-545G>A		intron	N/A	NP_476437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.166-545G>A		intron	N/A	ENSP00000346887.3
	CYP3A43	ENST00000222382.5	TSL:1	c.166-545G>A		intron	N/A	ENSP00000222382.5
	CYP3A43	ENST00000312017.9	TSL:1	c.166-545G>A		intron	N/A	ENSP00000312110.5

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85916 AN: 151862 Hom.: 26465 Cov.: 32

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.469 AC: 363438 AN: 774240 Hom.: 86785 AF XY: 0.467 AC XY: 181007 AN XY: 387278

African (AFR) AF: 0.851 AC: 12764 AN: 14994

American (AMR) AF: 0.423 AC: 6698 AN: 15834

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 4850 AN: 9838

East Asian (EAS) AF: 0.340 AC: 3168 AN: 9314

South Asian (SAS) AF: 0.474 AC: 26854 AN: 56666

European-Finnish (FIN) AF: 0.482 AC: 5158 AN: 10710

Middle Eastern (MID) AF: 0.376 AC: 1255 AN: 3338

European-Non Finnish (NFE) AF: 0.463 AC: 288923 AN: 624658

Other (OTH) AF: 0.477 AC: 13768 AN: 28888

GnomAD4 genome AF: 0.566 AC: 86020 AN: 151980 Hom.: 26514 Cov.: 32 AF XY: 0.562 AC XY: 41800 AN XY: 74316

African (AFR) AF: 0.832 AC: 34506 AN: 41488

American (AMR) AF: 0.463 AC: 7061 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1701 AN: 3462

East Asian (EAS) AF: 0.349 AC: 1802 AN: 5164

South Asian (SAS) AF: 0.492 AC: 2364 AN: 4806

European-Finnish (FIN) AF: 0.481 AC: 5086 AN: 10578

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31767 AN: 67908

Other (OTH) AF: 0.523 AC: 1104 AN: 2110

Alfa AF: 0.495 Hom.: 32852

Bravo AF: 0.574

Asia WGS AF: 0.480 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs800672; hg19: chr7-99436198;