8-60189993-CAAAAA-CAAAA

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 0 publications found

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]

CA8 Gene-Disease associations (from GenCC):

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• cerebellar ataxia

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• cerebellar ataxia, intellectual disability, and dysequilibrium

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004056.6. 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
	CA8	NM_004056.6	MANE Select	c.*36-9delT		intron	N/A	NP_004047.3
	CA8	NM_001321839.2		c.*36-9delT		intron	N/A	NP_001308768.1
	CA8	NR_135821.2		n.1212-9delT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA8	ENST00000317995.5	TSL:1 MANE Select	c.*36-9delT		intron	N/A	ENSP00000314407.4	P35219
	CA8	ENST00000943617.1		c.*36-12delT		intron	N/A	ENSP00000613676.1
	CA8	ENST00000943619.1		c.*36-9delT		intron	N/A	ENSP00000613678.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.397 AC: 13802 AN: 34752

American (AMR) AF: 0.0788 AC: 761 AN: 9656

Ashkenazi Jewish (ASJ) AF: 0.0849 AC: 216 AN: 2544

East Asian (EAS) AF: 0.0905 AC: 323 AN: 3568

South Asian (SAS) AF: 0.146 AC: 502 AN: 3436

European-Finnish (FIN) AF: 0.145 AC: 841 AN: 5802

Middle Eastern (MID) AF: 0.0859 AC: 17 AN: 198

European-Non Finnish (NFE) AF: 0.0408 AC: 1920 AN: 47096

Other (OTH) AF: 0.144 AC: 212 AN: 1470

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs57677078; hg19: chr8-61102552;