Genetic Variant CA3-AS1:n.59G>C (chr8-85463952-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000754494.1(CA3-AS1):n.59G>C 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 0.0000144 in 973,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CA3-AS1
ENST00000754494.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

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>C	intron	N/A
CA3-AS1	NR_121631.1		n.106+276G>C	intron	N/A
CA2	NM_000067.3	MANE Select	c.-130C>G	upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000146

AC:

AN:

821782

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

426148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19518

American (AMR)

AF:

0.00

AC:

AN:

34330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21276

East Asian (EAS)

AF:

0.0000309

AC:

AN:

32332

South Asian (SAS)

AF:

0.00

AC:

AN:

67318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33828

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3626

European-Non Finnish (NFE)

AF:

0.0000175

AC:

AN:

570296

Other (OTH)

AF:

0.0000255

AC:

AN:

39258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000132

AC:

AN:

151802

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41350

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5112

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67892

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

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:

0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-0.061

PromoterAI

-0.0063

Neutral

(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