NM_001216.3:c.*100C>A

Variant names:

• chr9-35681125-C-A
• rs1048638
• NM_001216.3:c.*100C>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 18 publications found

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]

ACMG classification

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	c.*100C>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000378357.9	NP_001207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA9	ENST00000378357.9	c.*100C>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_001216.3	ENSP00000367608.4
CA9	ENST00000485665.1	n.295C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
CA9	ENST00000493245.1	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.: 32

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.: 9 AF XY: 0.226 AC XY: 71839 AN XY: 317840

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

GnomAD4 genome AF: 0.193 AC: 29354 AN: 152152 Hom.: 3376 Cov.: 32 AF XY: 0.196 AC XY: 14551 AN XY: 74352

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: 73 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16555 AN: 67990

Other (OTH) AF: 0.213 AC: 451 AN: 2116

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
DANN	Benign	0.52
PhyloP100		0.28
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: rs1048638; hg19: chr9-35681122; COSMIC: COSV61407584; COSMIC: COSV61407584;