rs1048638

Positions:

• chr9-35681125-C-A
• chr9-35681125-C-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CA9	NM_001216.3	c.*100C>A		3_prime_UTR_variant	11/11	ENST00000378357.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA9	ENST00000378357.9	c.*100C>A		3_prime_UTR_variant	11/11	1	NM_001216.3	P1
CA9	ENST00000485665.1	n.295C>A		non_coding_transcript_exon_variant	2/2	2
CA9	ENST00000493245.1	n.684C>A		non_coding_transcript_exon_variant	7/7	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

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.0584

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.226

Gnomad4 OTH exome AF: 0.217

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

Gnomad4 AFR AF: 0.0711

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.213

Alfa AF: 0.173 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

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

LitVar

Other links and lift over

dbSNP: rs1048638; hg19: chr9-35681122; COSMIC: COSV61407584; COSMIC: COSV61407584;