9-35680340-C-G

Variant names:

• chr9-35680340-C-G
• rs3750431
• NM_001216.3:c.1237+201C>G

Variant summary

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

The NM_001216.3(CA9):​c.1237+201C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,588 control chromosomes in the GnomAD database, including 3,609 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 0.20 (3609 hom., cov: 32)
• Consequence: CA9 NM_001216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 14 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA9	NM_001216.3	c.1237+201C>G		intron_variant	Intron 9 of 10	ENST00000378357.9	NP_001207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA9	ENST00000378357.9	c.1237+201C>G		intron_variant	Intron 9 of 10	1	NM_001216.3	ENSP00000367608.4
CA9	ENST00000493245.1	n.441+201C>G		intron_variant	Intron 5 of 6	5

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29870 AN: 151470 Hom.: 3613 Cov.: 32

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 29845 AN: 151588 Hom.: 3609 Cov.: 32 AF XY: 0.196 AC XY: 14513 AN XY: 74114

African (AFR) AF: 0.0548 AC: 2245 AN: 40974

American (AMR) AF: 0.260 AC: 3966 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1019 AN: 5180

South Asian (SAS) AF: 0.195 AC: 939 AN: 4812

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10568

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17954 AN: 67992

Other (OTH) AF: 0.194 AC: 408 AN: 2106

Alfa AF: 0.101 Hom.: 162

Bravo AF: 0.193

Asia WGS AF: 0.184 AC: 640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.1
DANN	Benign	0.77
PhyloP100		0.43
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: rs3750431; hg19: chr9-35680337;