Genetic Variant CA1:c.37+532G>A (chr8-85341067-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.37+532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,240 control chromosomes in the GnomAD database, including 25,941 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 0.58 ( 25869 hom., cov: 30)

Exomes 𝑓: 0.54 ( 72 hom. )

Consequence

CA1
NM_001128831.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.205

Publications

1 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4 link	c.37+532G>A		intron_variant	Intron 2 of 7	ENST00000523022.6	NP_001122303.1	P00915V9HWE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6 link	c.37+532G>A		intron_variant	Intron 2 of 7	1	NM_001128831.4	ENSP00000429798.1		P00915

Frequencies

GnomAD3 genomes

AF:

0.580

AC:

88013

AN:

151640

Hom.:

25850

Cov.:

show subpopulations

Gnomad AFR

AF:

0.575

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.545

Gnomad ASJ

AF:

0.577

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.700

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.609

GnomAD4 exome

AF:

0.535

AC:

259

AN:

484

Hom.:

Cov.:

AF XY:

0.556

AC XY:

219

AN XY:

394

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

East Asian (EAS)

AF:

0.273

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.566

AC:

223

AN:

394

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.580

AC:

88064

AN:

151756

Hom.:

25869

Cov.:

AF XY:

0.582

AC XY:

43127

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.575

AC:

23775

AN:

41366

American (AMR)

AF:

0.544

AC:

8296

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

2000

AN:

3468

East Asian (EAS)

AF:

0.399

AC:

2051

AN:

5144

South Asian (SAS)

AF:

0.464

AC:

2228

AN:

4800

European-Finnish (FIN)

AF:

0.700

AC:

7369

AN:

10526

Middle Eastern (MID)

AF:

0.616

AC:

180

AN:

292

European-Non Finnish (NFE)

AF:

0.595

AC:

40422

AN:

67912

Other (OTH)

AF:

0.607

AC:

1278

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1809

3618

5428

7237

9046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

738

1476

2214

2952

3690

<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:

0.586

Hom.:

3136

Bravo

AF:

0.574

Asia WGS

AF:

0.410

AC:

1425

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.2

(source)

DANN

Benign

0.86

PhyloP100

0.20

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over