rs10098647

Positions:

• chr8-60192640-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004056.6(CA8):​c.*36-2655A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 151,914 control chromosomes in the GnomAD database, including 17,569 homozygotes. 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: 𝑓 0.47 (17569 hom., cov: 32)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA8	NM_004056.6	c.*36-2655A>G		intron_variant		ENST00000317995.5	NP_004047.3
CA8	NM_001321839.2	c.*36-2655A>G		intron_variant			NP_001308768.1
CA8	NR_135821.2	n.1212-2655A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA8	ENST00000317995.5	c.*36-2655A>G		intron_variant		1	NM_004056.6	ENSP00000314407	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70741 AN: 151794 Hom.: 17542 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.466 AC: 70815 AN: 151914 Hom.: 17569 Cov.: 32 AF XY: 0.467 AC XY: 34662 AN XY: 74224

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.494

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.477

Alfa AF: 0.408 Hom.: 12964

Bravo AF: 0.470

Asia WGS AF: 0.497 AC: 1724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.57

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: rs10098647; hg19: chr8-61105199;