chr8-85463952-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NR_121630.1(CA3-AS1):​n.334+630G>T variant causes a intron, non coding transcript 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
NR_121630.1 intron, non_coding_transcript

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0610
Variant links:
Genes affected
CA3-AS1 (HGNC:51657): (CA3 antisense RNA 1)
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BS2
High Homozygotes in GnomAdExome4 at 17 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CA3-AS1NR_121630.1 linkuse as main transcriptn.334+630G>T intron_variant, non_coding_transcript_variant
CA3-AS1NR_121631.1 linkuse as main transcriptn.106+276G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CA3-AS1ENST00000521761.6 linkuse as main transcriptn.334+630G>T intron_variant, non_coding_transcript_variant 4
CA3-AS1ENST00000517697.6 linkuse as main transcriptn.193+276G>T intron_variant, non_coding_transcript_variant 4
CA2ENST00000520127.5 linkuse as main transcript upstream_gene_variant 3 ENSP00000428443

Frequencies

GnomAD3 genomes
AF:
0.00408
AC:
619
AN:
151800
Hom.:
1
Cov.:
32
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.:
17
Cov.:
11
AF XY:
0.00487
AC XY:
2074
AN XY:
426136
show subpopulations
Gnomad4 AFR exome
AF:
0.000871
Gnomad4 AMR exome
AF:
0.00618
Gnomad4 ASJ exome
AF:
0.000658
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00120
Gnomad4 FIN exome
AF:
0.00160
Gnomad4 NFE exome
AF:
0.00638
Gnomad4 OTH exome
AF:
0.00469
GnomAD4 genome
AF:
0.00407
AC:
619
AN:
151906
Hom.:
1
Cov.:
32
AF XY:
0.00405
AC XY:
301
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.00154
Gnomad4 AMR
AF:
0.00850
Gnomad4 ASJ
AF:
0.000866
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00142
Gnomad4 NFE
AF:
0.00573
Gnomad4 OTH
AF:
0.00522
Alfa
AF:
0.00176
Hom.:
0
Bravo
AF:
0.00538
Asia WGS
AF:
0.00116
AC:
4
AN:
3464

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Osteopetrosis with renal tubular acidosis Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
CADD
Benign
15
DANN
Benign
0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs570970117; hg19: chr8-86376181; API