Genetic Variant CA1:c.-24-12998G>A (chr8-85354657-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001128831.4(CA1):c.-24-12998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 151,970 control chromosomes in the GnomAD database, including 26,940 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 0.59 ( 26940 hom., cov: 31)

Consequence

CA1
NM_001128831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0380

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CA1	NM_001128831.4	MANE Select	c.-24-12998G>A	intron	N/A	NP_001122303.1
CA1	NM_001128829.4		c.-99-4772G>A	intron	N/A	NP_001122301.1
CA1	NM_001128830.4		c.-101-11832G>A	intron	N/A	NP_001122302.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CA1	ENST00000523022.6	TSL:1 MANE Select	c.-24-12998G>A	intron	N/A	ENSP00000429798.1
CA1	ENST00000523953.5	TSL:1	c.-78-2873G>A	intron	N/A	ENSP00000430656.1
CA1	ENST00000524324.5	TSL:2	c.-24-12998G>A	intron	N/A	ENSP00000428923.1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89629

AN:

151852

Hom.:

26911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.661

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.535

Gnomad ASJ

AF:

0.563

Gnomad EAS

AF:

0.418

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.683

Gnomad MID

AF:

0.643

Gnomad NFE

AF:

0.569

Gnomad OTH

AF:

0.617

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

GnomAD4 genome

AF:

0.590

AC:

89709

AN:

151970

Hom.:

26940

Cov.:

AF XY:

0.591

AC XY:

43882

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.661

AC:

27413

AN:

41454

American (AMR)

AF:

0.535

AC:

8162

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

1954

AN:

3470

East Asian (EAS)

AF:

0.418

AC:

2157

AN:

5158

South Asian (SAS)

AF:

0.450

AC:

2166

AN:

4808

European-Finnish (FIN)

AF:

0.683

AC:

7201

AN:

10544

Middle Eastern (MID)

AF:

0.644

AC:

188

AN:

292

European-Non Finnish (NFE)

AF:

0.569

AC:

38699

AN:

67954

Other (OTH)

AF:

0.617

AC:

1301

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1860

3720

5581

7441

9301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.578

Hom.:

68031

Bravo

AF:

0.588

Asia WGS

AF:

0.419

AC:

1458

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.9

(source)

DANN

Benign

0.51

PhyloP100

0.038

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over