8-85463952-C-A

Position:

• chr8-85463952-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0610

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]

ACMG classification

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-AS1	NR_121630.1	n.334+630G>T		intron_variant, non_coding_transcript_variant
CA3-AS1	NR_121631.1	n.106+276G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA3-AS1	ENST00000521761.6	n.334+630G>T		intron_variant, non_coding_transcript_variant		4
CA3-AS1	ENST00000517697.6	n.193+276G>T		intron_variant, non_coding_transcript_variant		4
CA2	ENST00000520127.5			upstream_gene_variant		3		ENSP00000428443

Frequencies

GnomAD3 genomes AF: 0.00408 AC: 619 AN: 151800 Hom.: 1 Cov.: 32

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

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

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

Submissions by phenotype

Osteopetrosis with renal tubular acidosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 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

Other links and lift over

dbSNP: rs570970117; hg19: chr8-86376181;