Genetic Variant CA3-AS1:n.59G>T (chr8-85463952-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000754494.1(CA3-AS1):n.59G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 973,664 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0041 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 17 hom. )

Consequence

CA3-AS1
ENST00000754494.1 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610

Publications

0 publications found

Variant links:

Genes affected

CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)

CA3-AS1 links:

CA2 (HGNC:1373): (carbonic anhydrase 2) The protein encoded by this gene is one of several isozymes of carbonic anhydrase, which catalyzes reversible hydration of carbon dioxide. Defects in this enzyme are associated with osteopetrosis and renal tubular acidosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

CA2 Gene-Disease associations (from GenCC):

autosomal recessive osteopetrosis 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

CA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BS2

High Homozygotes in GnomAdExome4 at 17 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000754494.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CA3-AS1	NR_121630.1		n.334+630G>T	intron	N/A
CA3-AS1	NR_121631.1		n.106+276G>T	intron	N/A
CA2	NM_000067.3	MANE Select	c.-130C>A	upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CA3-AS1	ENST00000754494.1		n.59G>T	non_coding_transcript_exon	Exon 1 of 3
CA3-AS1	ENST00000517697.7	TSL:4	n.193+276G>T	intron	N/A
CA3-AS1	ENST00000521761.6	TSL:4	n.334+630G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00408

AC:

619

AN:

151800

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00142

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00573

Gnomad OTH

AF:

0.00528

GnomAD4 exome

AF:

0.00512

AC:

4205

AN:

821758

Hom.:

Cov.:

AF XY:

0.00487

AC XY:

2074

AN XY:

426136

show subpopulations

African (AFR)

AF:

0.000871

AC:

AN:

19518

American (AMR)

AF:

0.00618

AC:

212

AN:

34330

Ashkenazi Jewish (ASJ)

AF:

0.000658

AC:

AN:

21276

East Asian (EAS)

AF:

0.00

AC:

AN:

32332

South Asian (SAS)

AF:

0.00120

AC:

AN:

67318

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

33828

Middle Eastern (MID)

AF:

0.000552

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.00638

AC:

3641

AN:

570272

Other (OTH)

AF:

0.00469

AC:

184

AN:

39258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

209

418

627

836

1045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00407

AC:

619

AN:

151906

Hom.:

Cov.:

AF XY:

0.00405

AC XY:

301

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41466

American (AMR)

AF:

0.00850

AC:

130

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000866

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00145

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00142

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00573

AC:

389

AN:

67880

Other (OTH)

AF:

0.00522

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

102

136

170

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:

0.00176

Hom.:

Bravo

AF:

0.00538

Asia WGS

AF:

0.00116

AC:

AN:

3464

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Osteopetrosis with renal tubular acidosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.061

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=289/11

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

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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