Genetic Variant NM_057095.3:c.*194A>G (chr7-99866195-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_057095.3(CYP3A43):c.*194A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 345,052 control chromosomes in the GnomAD database, including 1,236 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 0.066 ( 1029 hom., cov: 32)

Exomes 𝑓: 0.014 ( 207 hom. )

Consequence

CYP3A43
NM_057095.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.16

Publications

3 publications found

Variant links:

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]

CYP3A43 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP3A43	NM_057095.3	MANE Select	c.*194A>G	downstream_gene	N/A	NP_476436.1
CYP3A43	NM_022820.5		c.*194A>G	downstream_gene	N/A	NP_073731.1
CYP3A43	NM_057096.4		c.*280A>G	downstream_gene	N/A	NP_476437.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.*194A>G	downstream_gene	N/A	ENSP00000346887.3
CYP3A43	ENST00000222382.5	TSL:1	c.*194A>G	downstream_gene	N/A	ENSP00000222382.5
CYP3A43	ENST00000312017.9	TSL:1	c.*280A>G	downstream_gene	N/A	ENSP00000312110.5

Frequencies

GnomAD3 genomes

AF:

0.0659

AC:

10024

AN:

152100

Hom.:

1028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.0580

GnomAD4 exome

AF:

0.0136

AC:

2617

AN:

192834

Hom.:

207

AF XY:

0.0124

AC XY:

1232

AN XY:

98974

show subpopulations

African (AFR)

AF:

0.241

AC:

1487

AN:

6170

American (AMR)

AF:

0.0524

AC:

294

AN:

5612

Ashkenazi Jewish (ASJ)

AF:

0.00402

AC:

AN:

7210

East Asian (EAS)

AF:

0.000352

AC:

AN:

17054

South Asian (SAS)

AF:

0.00998

AC:

AN:

5512

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13976

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

1510

European-Non Finnish (NFE)

AF:

0.00272

AC:

335

AN:

123062

Other (OTH)

AF:

0.0299

AC:

380

AN:

12728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

195

293

390

488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0660

AC:

10051

AN:

152218

Hom.:

1029

Cov.:

AF XY:

0.0638

AC XY:

4749

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.221

AC:

9176

AN:

41492

American (AMR)

AF:

0.0343

AC:

524

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00462

AC:

AN:

3460

East Asian (EAS)

AF:

0.000770

AC:

AN:

5192

South Asian (SAS)

AF:

0.00745

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00234

AC:

159

AN:

68014

Other (OTH)

AF:

0.0588

AC:

124

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

395

791

1186

1582

1977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0230

Hom.:

1205

Bravo

AF:

0.0775

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.044

(source)

DANN

Benign

0.32

PhyloP100

-2.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over