Variant rs12553173 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001216.3(CA9):c.145T>C(p.Leu49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,613,850 control chromosomes in the GnomAD database, including 19,483 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 ( 4006 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15477 hom. )

Consequence

CA9
NM_001216.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.26

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:

ARHGEF39 (HGNC:25909): (Rho guanine nucleotide exchange factor 39) Predicted to enable guanyl-nucleotide exchange factor activity. Involved in positive regulation of cell migration. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARHGEF39 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CA9	NM_001216.3 linkuse as main transcript	c.145T>C	p.Leu49=	synonymous_variant	1/11	ENST00000378357.9	NP_001207.2
CA9	XM_047423849.1 linkuse as main transcript	c.145T>C	p.Leu49=	synonymous_variant	1/6		XP_047279805.1
CA9	XM_047423850.1 linkuse as main transcript	c.145T>C	p.Leu49=	synonymous_variant	1/6		XP_047279806.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA9	ENST00000378357.9 linkuse as main transcript	c.145T>C	p.Leu49=	synonymous_variant	1/11	1	NM_001216.3	ENSP00000367608	P1
ARHGEF39	ENST00000490638.5 linkuse as main transcript	c.-389A>G		5_prime_UTR_variant, NMD_transcript_variant	1/12	1		ENSP00000436756		Q8N4T4-2

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

30238

AN:

151904

Hom.:

3987

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.0654

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.0987

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.140

AC:

35150

AN:

251306

Hom.:

3229

AF XY:

0.133

AC XY:

18038

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0653

Gnomad EAS exome

AF:

0.169

Gnomad SAS exome

AF:

0.0919

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.138

AC:

201253

AN:

1461828

Hom.:

15477

Cov.:

AF XY:

0.136

AC XY:

98650

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.0647

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.0956

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.137

Gnomad4 OTH exome

AF:

0.143

GnomAD4 genome

AF:

0.199

AC:

30319

AN:

152022

Hom.:

4006

Cov.:

AF XY:

0.195

AC XY:

14477

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.132

Gnomad4 ASJ

AF:

0.0654

Gnomad4 EAS

AF:

0.167

Gnomad4 SAS

AF:

0.0990

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.174

Alfa

AF:

0.158

Hom.:

1612

Bravo

AF:

0.211

Asia WGS

AF:

0.150

AC:

521

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.128

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.062

DANN

Benign

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over