rs7821248

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001128831.4(CA1):c.428C>T(p.Ala143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,611,646 control chromosomes in the GnomAD database, including 340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 184 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 156 hom. )

Consequence

CA1
NM_001128831.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.38

Publications

12 publications found

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]

CA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006014228).

BP6

Variant 8-85333547-G-A is Benign according to our data. Variant chr8-85333547-G-A is described in ClinVar as [Benign]. Clinvar id is 776361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4 link	c.428C>T	p.Ala143Val	missense_variant	Exon 5 of 8	ENST00000523022.6	NP_001122303.1	P00915V9HWE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6 link	c.428C>T	p.Ala143Val	missense_variant	Exon 5 of 8	1	NM_001128831.4	ENSP00000429798.1		P00915

Frequencies

GnomAD3 genomes

AF:

0.0267

AC:

4066

AN:

152138

Hom.:

181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0925

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0253

GnomAD2 exomes

AF:

0.00683

AC:

1713

AN:

250640

AF XY:

0.00490

show subpopulations

Gnomad AFR exome

AF:

0.0919

Gnomad AMR exome

AF:

0.00475

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000230

Gnomad OTH exome

AF:

0.00262

GnomAD4 exome

AF:

0.00283

AC:

4136

AN:

1459388

Hom.:

156

Cov.:

AF XY:

0.00250

AC XY:

1815

AN XY:

726126

show subpopulations

African (AFR)

AF:

0.0961

AC:

3206

AN:

33368

American (AMR)

AF:

0.00550

AC:

246

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.000537

AC:

AN:

26090

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39574

South Asian (SAS)

AF:

0.000383

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53298

Middle Eastern (MID)

AF:

0.00782

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000156

AC:

173

AN:

1110126

Other (OTH)

AF:

0.00693

AC:

418

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

192

384

577

769

961

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0268

AC:

4086

AN:

152258

Hom.:

184

Cov.:

AF XY:

0.0254

AC XY:

1891

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0928

AC:

3852

AN:

41526

American (AMR)

AF:

0.0105

AC:

160

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68024

Other (OTH)

AF:

0.0250

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

191

382

573

764

955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.0300

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0865

AC:

381

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00850

AC:

1032

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;T;T;T;T;T;.;T;.;T;T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.060

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.93

.;.;.;.;D;D;D;D;D;D;D;.;D;D

MetaRNN

Benign

0.0060

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

.;M;M;M;M;.;.;.;.;.;.;.;.;.

PhyloP100

3.4

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.7

.;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.013

.;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.011

D;T;T;T;T;D;.;D;.;.;.;.;T;.

Polyphen

0.96

.;D;D;D;D;.;.;.;.;.;.;.;.;.

Vest4

0.32

MVP

0.83

MPC

0.040

ClinPred

0.071

GERP RS

2.2

Varity_R

0.56

gMVP

0.82

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over