7-99844340-A-G

Variant names:

• chr7-99844340-A-G
• rs501275
• NM_057095.3:c.318+98A>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.318+98A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 1,153,240 control chromosomes in the GnomAD database, including 11,684 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 (5831 hom., cov: 32)
  • Exomes 𝑓: 0.078 (5853 hom.)
• Consequence: CYP3A43 NM_057095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 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.318+98A>G		intron	N/A	NP_476436.1	Q9HB55-1
	CYP3A43	NM_022820.5		c.318+98A>G		intron	N/A	NP_073731.1	Q9HB55-2
	CYP3A43	NM_057096.4		c.318+98A>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.318+98A>G		intron	N/A	ENSP00000346887.3	Q9HB55-1
	CYP3A43	ENST00000222382.5	TSL:1	c.318+98A>G		intron	N/A	ENSP00000222382.5	Q9HB55-2
	CYP3A43	ENST00000312017.9	TSL:1	c.318+98A>G		intron	N/A	ENSP00000312110.5	Q9HB55-3

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29563 AN: 152084 Hom.: 5810 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.0777 AC: 77767 AN: 1001038 Hom.: 5853 AF XY: 0.0769 AC XY: 39224 AN XY: 510056

African (AFR) AF: 0.529 AC: 11854 AN: 22422

American (AMR) AF: 0.0988 AC: 2960 AN: 29954

Ashkenazi Jewish (ASJ) AF: 0.0923 AC: 2062 AN: 22338

East Asian (EAS) AF: 0.000453 AC: 15 AN: 33098

South Asian (SAS) AF: 0.0746 AC: 5002 AN: 67020

European-Finnish (FIN) AF: 0.0607 AC: 2838 AN: 46718

Middle Eastern (MID) AF: 0.108 AC: 344 AN: 3194

European-Non Finnish (NFE) AF: 0.0662 AC: 48405 AN: 731640

Other (OTH) AF: 0.0960 AC: 4287 AN: 44654

GnomAD4 genome AF: 0.195 AC: 29633 AN: 152202 Hom.: 5831 Cov.: 32 AF XY: 0.189 AC XY: 14091 AN XY: 74420

African (AFR) AF: 0.510 AC: 21156 AN: 41480

American (AMR) AF: 0.124 AC: 1895 AN: 15294

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

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4830

European-Finnish (FIN) AF: 0.0584 AC: 619 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0702 AC: 4778 AN: 68016

Other (OTH) AF: 0.170 AC: 358 AN: 2112

Alfa AF: 0.105 Hom.: 1813

Bravo AF: 0.213

Asia WGS AF: 0.0600 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.5
DANN	Benign	0.27
PhyloP100		-0.20
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: rs501275; hg19: chr7-99441963;