rs371314891

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128831.4(CA1):ā€‹c.719T>Gā€‹(p.Val240Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

CA1
NM_001128831.4 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.448
Variant links:
Genes affected
CA1 (HGNC:1368): (carbonic anhydrase 1) 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. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08520827).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CA1NM_001128831.4 linkc.719T>G p.Val240Gly missense_variant Exon 8 of 8 ENST00000523022.6 NP_001122303.1 P00915V9HWE3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CA1ENST00000523022.6 linkc.719T>G p.Val240Gly missense_variant Exon 8 of 8 1 NM_001128831.4 ENSP00000429798.1 P00915

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250922
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135618
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459338
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726014
show subpopulations
Gnomad4 AFR exome
AF:
0.0000599
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000193
Hom.:
0
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
18
DANN
Benign
0.47
DEOGEN2
Benign
0.061
T;T;T;T;T;T;T;.;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.32
.;.;.;.;T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.085
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
.;L;L;L;L;.;.;.;.
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.8
.;N;N;N;N;N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.41
.;T;T;T;T;T;T;T;T
Sift4G
Benign
0.39
T;T;T;T;T;T;.;T;.
Polyphen
0.32
.;B;B;B;B;.;.;.;.
Vest4
0.16
MVP
0.41
MPC
0.067
ClinPred
0.048
T
GERP RS
-0.64
Varity_R
0.17
gMVP
0.40

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.

Other links and lift over

dbSNP: rs371314891; hg19: chr8-86240856; API