8-60189993-CAAAAA-CAAAA

Variant names:

• chr8-60189993-CA-C
• rs57677078
• NM_004056.6:c.*36-9delT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_004056.6(CA8):​c.*36-9delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 109,126 control chromosomes in the GnomAD database, including 2,452 homozygotes. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2452 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.153

Genes affected

CA8 (HGNC:1382): (carbonic anhydrase 8) The protein encoded by this gene was initially named CA-related protein because of sequence similarity to other known carbonic anhydrase genes. However, the gene product lacks carbonic anhydrase activity (i.e., the reversible hydration of carbon dioxide). The gene product continues to carry a carbonic anhydrase designation based on clear sequence identity to other members of the carbonic anhydrase gene family. The absence of CA8 gene transcription in the cerebellum of the lurcher mutant in mice with a neurologic defect suggests an important role for this acatalytic form. Mutations in this gene are associated with cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CMARQ3). Polymorphisms in this gene are associated with osteoporosis, and overexpression of this gene in osteosarcoma cells suggests an oncogenic role. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 8-60189993-CA-C is Benign according to our data. Variant chr8-60189993-CA-C is described in Lovd as [Benign]. Variant chr8-60189993-CA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA8	NM_004056.6	c.*36-9delT		intron_variant	Intron 8 of 8	ENST00000317995.5	NP_004047.3
CA8	NM_001321839.2	c.*36-9delT		intron_variant	Intron 7 of 7		NP_001308768.1
CA8	NR_135821.2	n.1212-9delT		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA8	ENST00000317995.5	c.*36-9delT		intron_variant	Intron 8 of 8	1	NM_004056.6	ENSP00000314407.4

Frequencies

GnomAD3 genomes AF: 0.170 AC: 18574 AN: 109088 Hom.: 2449 Cov.: 26

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0182

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0849

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0841

Gnomad NFE AF: 0.0408

Gnomad OTH AF: 0.142

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.170 AC: 18605 AN: 109126 Hom.: 2452 Cov.: 26 AF XY: 0.174 AC XY: 9076 AN XY: 52170

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.0788

Gnomad4 ASJ AF: 0.0849

Gnomad4 EAS AF: 0.0905

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.0408

Gnomad4 OTH AF: 0.144

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs57677078; hg19: chr8-61102552;