Genetic Variant CA5B:p.Glu211Gly (chrX-15776727-A-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.632A>G(p.Glu211Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,207,574 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 3 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 1 hem. )

Consequence

CA5B
NM_007220.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.81

Publications

1 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 GnomAd4 at 3 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	NM_007220.4	MANE Select	c.632A>G	p.Glu211Gly	missense	Exon 7 of 8	NP_009151.1	Q9Y2D0
	CA5BP1-CA5B	NR_160544.1		n.2047A>G		non_coding_transcript_exon	Exon 11 of 12

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA5B	ENST00000318636.8	TSL:1 MANE Select	c.632A>G	p.Glu211Gly	missense	Exon 7 of 8	ENSP00000314099.3	Q9Y2D0
	CA5B	ENST00000948118.1		c.632A>G	p.Glu211Gly	missense	Exon 7 of 9	ENSP00000618177.1

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111605

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

182647

AF XY:

0.0000447

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000665

GnomAD4 exome

AF:

0.00000912

AC:

AN:

1095969

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361367

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26364

American (AMR)

AF:

0.0000284

AC:

AN:

35171

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30196

South Asian (SAS)

AF:

0.00

AC:

AN:

54055

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40522

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.00000595

AC:

AN:

840171

Other (OTH)

AF:

0.0000652

AC:

AN:

46010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

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:

0.0000448

AC:

AN:

111605

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

33771

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30666

American (AMR)

AF:

0.0000952

AC:

AN:

10504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2636

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53114

Other (OTH)

AF:

0.00

AC:

AN:

1486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

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

0.14

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.094

M_CAP

Pathogenic

0.56

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.2

PhyloP100

5.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.7

REVEL

Benign

0.24

Sift

Benign

0.11

Sift4G

Benign

0.28

Polyphen

0.27

Vest4

0.55

MutPred

0.40

Loss of stability (P = 0.055)

MVP

0.92

MPC

0.39

ClinPred

0.15

GERP RS

5.7

Varity_R

0.47

gMVP

0.68

Mutation Taster

=67/33

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over