rs28669087

Variant names:

• chr7-99848351-G-A
• rs28669087
• NM_057095.3:c.521+97G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-99848351-G-A
• chr7-99848351-G-C
• chr7-99848351-G-T

Variant summary

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

The NM_057095.3(CYP3A43):​c.521+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00515 in 1,314,736 control chromosomes in the GnomAD database, including 278 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 0.025 (152 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (126 hom.)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 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.521+97G>A		intron	N/A	NP_476436.1
	CYP3A43	NM_022820.5		c.521+97G>A		intron	N/A	NP_073731.1
	CYP3A43	NM_057096.4		c.521+97G>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.521+97G>A		intron	N/A	ENSP00000346887.3
	CYP3A43	ENST00000222382.5	TSL:1	c.521+97G>A		intron	N/A	ENSP00000222382.5
	CYP3A43	ENST00000312017.9	TSL:1	c.521+97G>A		intron	N/A	ENSP00000312110.5

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 3730 AN: 152116 Hom.: 152 Cov.: 32

Gnomad AFR AF: 0.0856

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.00261 AC: 3030 AN: 1162502 Hom.: 126 AF XY: 0.00228 AC XY: 1324 AN XY: 581584

African (AFR) AF: 0.0872 AC: 2337 AN: 26810

American (AMR) AF: 0.00448 AC: 158 AN: 35244

Ashkenazi Jewish (ASJ) AF: 0.00511 AC: 116 AN: 22712

East Asian (EAS) AF: 0.00 AC: 0 AN: 34832

South Asian (SAS) AF: 0.000179 AC: 13 AN: 72556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48688

Middle Eastern (MID) AF: 0.00413 AC: 15 AN: 3636

European-Non Finnish (NFE) AF: 0.000127 AC: 110 AN: 868294

Other (OTH) AF: 0.00565 AC: 281 AN: 49730

GnomAD4 genome AF: 0.0246 AC: 3744 AN: 152234 Hom.: 152 Cov.: 32 AF XY: 0.0234 AC XY: 1744 AN XY: 74442

African (AFR) AF: 0.0858 AC: 3561 AN: 41516

American (AMR) AF: 0.00602 AC: 92 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68014

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0215 Hom.: 11

Bravo AF: 0.0282

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		-0.11
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: rs28669087; hg19: chr7-99445974; COSMIC: COSV55937369;