8-85463769-AGGAGCCCCGGAGCCCCGGAGCCCC-AGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCC

Variant names:

• chr8-85463769-A-AGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCC
• rs77895131
• ENST00000654303.1:n.32_33insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC

Variant summary

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

The ENST00000654303.1(CA3-AS1):​n.32_33insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC 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 0.0000233 in 85,810 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: not found (cov: 0)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: CA3-AS1 ENST00000654303.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 0 publications found

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]

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA3-AS1	NR_121630.1		n.334+812_334+813insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC		intron	N/A
	CA3-AS1	NR_121631.1		n.106+458_106+459insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC		intron	N/A
	CA2	NM_000067.3	MANE Select	c.-313_-312insGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCCGGAGCCCC		upstream_gene	N/A	NP_000058.1	P00918

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA3-AS1	ENST00000654303.1		n.32_33insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC		non_coding_transcript_exon	Exon 1 of 3
	CA3-AS1	ENST00000517697.7	TSL:4	n.193+458_193+459insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC		intron	N/A
	CA3-AS1	ENST00000521761.6	TSL:4	n.334+812_334+813insGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCCGGGGCTCC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000233 AC: 2 AN: 85810 Hom.: 0 AF XY: 0.0000425 AC XY: 2 AN XY: 47016

African (AFR) AF: 0.00 AC: 0 AN: 966

American (AMR) AF: 0.00 AC: 0 AN: 992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2268

East Asian (EAS) AF: 0.00 AC: 0 AN: 4344

South Asian (SAS) AF: 0.00 AC: 0 AN: 15286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 338

European-Non Finnish (NFE) AF: 0.0000384 AC: 2 AN: 52038

Other (OTH) AF: 0.00 AC: 0 AN: 4856

GnomAD4 genome Cov.: 0

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

Other links and lift over

dbSNP: rs77895131; hg19: chr8-86375998;