8-60189993-CAAAAA-CAAA

Variant names:

• chr8-60189993-CAA-C
• rs57677078
• NM_004056.6:c.*36-10_*36-9delTT

Variant summary

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

The NM_004056.6(CA8):​c.*36-10_*36-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 109,168 control chromosomes in the GnomAD database, including 75 homozygotes. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.026 (75 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-CAA-C is Benign according to our data. Variant chr8-60189993-CAA-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA8	NM_004056.6	c.*36-10_*36-9delTT		intron_variant	Intron 8 of 8	ENST00000317995.5	NP_004047.3
CA8	NM_001321839.2	c.*36-10_*36-9delTT		intron_variant	Intron 7 of 7		NP_001308768.1
CA8	NR_135821.2	n.1212-10_1212-9delTT		intron_variant	Intron 9 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA8	ENST00000317995.5	c.*36-10_*36-9delTT		intron_variant	Intron 8 of 8	1	NM_004056.6	ENSP00000314407.4

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 2850 AN: 109126 Hom.: 76 Cov.: 26

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0151

Gnomad ASJ AF: 0.000393

Gnomad EAS AF: 0.00195

Gnomad SAS AF: 0.0217

Gnomad FIN AF: 0.00502

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.0138

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0262 AC: 2865 AN: 109168 Hom.: 75 Cov.: 26 AF XY: 0.0268 AC XY: 1397 AN XY: 52200

Gnomad4 AFR AF: 0.0726

Gnomad4 AMR AF: 0.0151

Gnomad4 ASJ AF: 0.000393

Gnomad4 EAS AF: 0.00196

Gnomad4 SAS AF: 0.0218

Gnomad4 FIN AF: 0.00502

Gnomad4 NFE AF: 0.00130

Gnomad4 OTH AF: 0.0143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;