Genetic Variant CA3-AS1:n.1_32dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC (chr8-85463769-A-AGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000654303.1(CA3-AS1):n.1_32dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC 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 0.0000473 in 232,396 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000068 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CA3-AS1
ENST00000654303.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00800

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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000654303.1. 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+781_334+812dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC	intron	N/A
CA3-AS1	NR_121631.1		n.106+427_106+458dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC	intron	N/A
CA2	NM_000067.3	MANE Select	c.-313_-312insGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCC	upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CA3-AS1	ENST00000654303.1		n.1_32dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC	non_coding_transcript_exon	Exon 1 of 3
CA3-AS1	ENST00000517697.7	TSL:4	n.193+427_193+458dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC	intron	N/A
CA3-AS1	ENST00000521761.6	TSL:4	n.334+781_334+812dupGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000682

AC:

AN:

146586

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000606

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

85810

Hom.:

AF XY:

0.00

AC XY:

AN XY:

47016

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

966

American (AMR)

AF:

0.00

AC:

AN:

992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2268

East Asian (EAS)

AF:

0.00

AC:

AN:

4344

South Asian (SAS)

AF:

0.00

AC:

AN:

15286

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4722

Middle Eastern (MID)

AF:

0.00

AC:

AN:

338

European-Non Finnish (NFE)

AF:

0.0000192

AC:

AN:

52038

Other (OTH)

AF:

0.00

AC:

AN:

4856

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000682

AC:

AN:

146586

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

71412

show subpopulations

African (AFR)

AF:

0.000126

AC:

AN:

39648

American (AMR)

AF:

0.00

AC:

AN:

14988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4816

South Asian (SAS)

AF:

0.000213

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000606

AC:

AN:

65996

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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.:

792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0080

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over