chr8-60237172-C-T

Position:

• chr8-60237172-C-T

Variant summary

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

The NM_004056.6(CA8):​c.418-4793G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 151,996 control chromosomes in the GnomAD database, including 21,703 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 0.53 (21703 hom., cov: 32)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA8	NM_004056.6	c.418-4793G>A		intron_variant		ENST00000317995.5	NP_004047.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA8	ENST00000317995.5	c.418-4793G>A		intron_variant		1	NM_004056.6	ENSP00000314407	P1
CA8	ENST00000524872.5	n.656-4793G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80321 AN: 151878 Hom.: 21670 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.529 AC: 80399 AN: 151996 Hom.: 21703 Cov.: 32 AF XY: 0.525 AC XY: 38990 AN XY: 74278

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.530

Alfa AF: 0.519 Hom.: 44584

Bravo AF: 0.528

Asia WGS AF: 0.473 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.74

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: rs6984526; hg19: chr8-61149731;