Genetic Variant NM_007220.4:c.202A>G (chrX-15764637-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_007220.4(CA5B):c.202A>G(p.Asn68Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000355 in 1,182,110 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 21)

Exomes 𝑓: 0.000037 ( 0 hom. 12 hem. )

Consequence

CA5B
NM_007220.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36296606).

BS2

High Hemizygotes in GnomAdExome4 at 12 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.202A>G	p.Asn68Asp	missense	Exon 3 of 8	NP_009151.1	Q9Y2D0
CA5BP1-CA5B	NR_160544.1		n.966A>G		non_coding_transcript_exon	Exon 6 of 12
CA5BP1-CA5B	NR_160545.1		n.966A>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.202A>G	p.Asn68Asp	missense	Exon 3 of 8	ENSP00000314099.3	Q9Y2D0
CA5B	ENST00000948118.1		c.202A>G	p.Asn68Asp	missense	Exon 3 of 9	ENSP00000618177.1
CA5B	ENST00000479740.5	TSL:3	c.202A>G	p.Asn68Asp	missense	Exon 2 of 3	ENSP00000417553.1	C9JA11

Frequencies

GnomAD3 genomes

AF:

0.0000183

AC:

AN:

109199

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000987

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:

0.0000191

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000130

AC:

AN:

153518

AF XY:

0.0000206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000285

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000373

AC:

AN:

1072911

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

348355

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25742

American (AMR)

AF:

0.00

AC:

AN:

31531

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17148

East Asian (EAS)

AF:

0.00

AC:

AN:

30126

South Asian (SAS)

AF:

0.00

AC:

AN:

48887

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39461

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3880

European-Non Finnish (NFE)

AF:

0.0000445

AC:

AN:

831138

Other (OTH)

AF:

0.0000667

AC:

AN:

44998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000183

AC:

AN:

109199

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

31485

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29877

American (AMR)

AF:

0.0000987

AC:

AN:

10127

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2612

East Asian (EAS)

AF:

0.00

AC:

AN:

3501

South Asian (SAS)

AF:

0.00

AC:

AN:

2493

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

52485

Other (OTH)

AF:

0.00

AC:

AN:

1446

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

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

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000826

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

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.15

PhyloP100

5.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.26

Sift

Benign

0.093

Sift4G

Benign

0.15

Polyphen

0.11

Vest4

0.18

MVP

0.88

MPC

3.5

ClinPred

0.21

GERP RS

5.5

Varity_R

0.50

gMVP

0.75

Mutation Taster

=60/40

polymorphism

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over