Genetic Variant CA9:c.*100C>A (chr9-35681125-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001216.3(CA9):c.*100C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 775,028 control chromosomes in the GnomAD database, including 20,138 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 ( 3376 hom., cov: 32)

Exomes 𝑓: 0.22 ( 16762 hom. )

Consequence

CA9
NM_001216.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.284

Publications

18 publications found

Variant links:

Genes affected

CA9 (HGNC:1383): (carbonic anhydrase 9) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12. [provided by RefSeq, Jun 2014]

CA9 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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA9	NM_001216.3 link	c.*100C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000378357.9	NP_001207.2	Q16790A0A0S2Z3D0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CA9	ENST00000378357.9 link	c.*100C>A	3_prime_UTR_variant	Exon 11 of 11	1	NM_001216.3	ENSP00000367608.4	Q16790
CA9	ENST00000485665.1 link	n.295C>A	non_coding_transcript_exon_variant	Exon 2 of 2	2
CA9	ENST00000493245.1 link	n.684C>A	non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29339

AN:

152034

Hom.:

3369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0713

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.0595

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.262

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.243

Gnomad OTH

AF:

0.213

GnomAD4 exome

AF:

0.223

AC:

138666

AN:

622876

Hom.:

16762

Cov.:

AF XY:

0.226

AC XY:

71839

AN XY:

317840

show subpopulations

African (AFR)

AF:

0.0714

AC:

1033

AN:

14476

American (AMR)

AF:

0.327

AC:

5697

AN:

17414

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

3389

AN:

14076

East Asian (EAS)

AF:

0.0584

AC:

1715

AN:

29376

South Asian (SAS)

AF:

0.287

AC:

9566

AN:

33378

European-Finnish (FIN)

AF:

0.252

AC:

9863

AN:

39188

Middle Eastern (MID)

AF:

0.288

AC:

631

AN:

2190

European-Non Finnish (NFE)

AF:

0.226

AC:

100191

AN:

442520

Other (OTH)

AF:

0.217

AC:

6581

AN:

30258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5137

10275

15412

20550

25687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2346

4692

7038

9384

11730

<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:

0.193

AC:

29354

AN:

152152

Hom.:

3376

Cov.:

AF XY:

0.196

AC XY:

14551

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.0711

AC:

2954

AN:

41524

American (AMR)

AF:

0.249

AC:

3806

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

816

AN:

3470

East Asian (EAS)

AF:

0.0594

AC:

308

AN:

5182

South Asian (SAS)

AF:

0.295

AC:

1424

AN:

4824

European-Finnish (FIN)

AF:

0.262

AC:

2761

AN:

10552

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.243

AC:

16555

AN:

67990

Other (OTH)

AF:

0.213

AC:

451

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1182

2364

3545

4727

5909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<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:

0.170

Hom.:

649

Bravo

AF:

0.184

Asia WGS

AF:

0.173

AC:

603

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.7

(source)

DANN

Benign

0.52

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over