8-85463952-C-T

Variant names:

• chr8-85463952-C-T
• rs570970117
• ENST00000754494.1:n.59G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000754494.1(CA3-AS1):​n.59G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CA3-AS1 ENST00000754494.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

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

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

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 821782 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 426148

African (AFR) AF: 0.00 AC: 0 AN: 19518

American (AMR) AF: 0.00 AC: 0 AN: 34330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21276

East Asian (EAS) AF: 0.00 AC: 0 AN: 32332

South Asian (SAS) AF: 0.00 AC: 0 AN: 67318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3626

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 570296

Other (OTH) AF: 0.00 AC: 0 AN: 39258

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		-0.061
PromoterAI		-0.033	Neutral

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

Other links and lift over

dbSNP: rs570970117; hg19: chr8-86376181;