Genetic Variant CA5B:p.Pro50Ala (chrX-15764583-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_007220.4(CA5B):c.148C>G(p.Pro50Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000722 in 1,205,724 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000077 ( 0 hom. 23 hem. )

Consequence

CA5B
NM_007220.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Publications

0 publications found

Variant links:

Genes affected

CA5B (HGNC:1378): (carbonic anhydrase 5B) 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 gene encodes carbonic anhydrase 5B. CA5B, and the related CA5A gene, has its expression localized in the mitochondria though CA5B has a wider tissue distribution than CA5A, which is restricted to the liver, kidneys, and skeletal muscle. A carbonic anhydrase pseudogene (CA5BP1) is adjacent to the CA5B gene and these two loci produce CA5BP1-CA5B readthrough transcripts. [provided by RefSeq, Jan 2019]

CA5B links:

CA5BP1-CA5B (HGNC:):

CA5BP1-CA5B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 23 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007220.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA5B	NM_007220.4	MANE Select	c.148C>G	p.Pro50Ala	missense	Exon 3 of 8	NP_009151.1	Q9Y2D0
CA5BP1-CA5B	NR_160544.1		n.912C>G		non_coding_transcript_exon	Exon 6 of 12
CA5BP1-CA5B	NR_160545.1		n.912C>G		non_coding_transcript_exon	Exon 6 of 6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CA5B	ENST00000318636.8	TSL:1 MANE Select	c.148C>G	p.Pro50Ala	missense	Exon 3 of 8	ENSP00000314099.3	Q9Y2D0
CA5B	ENST00000948118.1		c.148C>G	p.Pro50Ala	missense	Exon 3 of 9	ENSP00000618177.1
CA5B	ENST00000479740.5	TSL:3	c.148C>G	p.Pro50Ala	missense	Exon 2 of 3	ENSP00000417553.1	C9JA11

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

110584

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000567

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000278

AC:

AN:

179602

AF XY:

0.0000310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000500

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000767

AC:

AN:

1095140

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

360974

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26366

American (AMR)

AF:

0.0000285

AC:

AN:

35044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19101

East Asian (EAS)

AF:

0.00

AC:

AN:

30170

South Asian (SAS)

AF:

0.00

AC:

AN:

53533

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40403

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4078

European-Non Finnish (NFE)

AF:

0.0000964

AC:

AN:

840480

Other (OTH)

AF:

0.0000218

AC:

AN:

45965

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000271

AC:

AN:

110584

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32774

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30342

American (AMR)

AF:

0.00

AC:

AN:

10303

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2593

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5888

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

52881

Other (OTH)

AF:

0.00

AC:

AN:

1467

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.70

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.70

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.7

PhyloP100

5.8

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.53

MVP

0.76

MPC

0.86

ClinPred

0.69

GERP RS

5.2

Varity_R

0.31

gMVP

0.68

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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