rs10216440

Positions:

• chr8-60273163-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.292+6526A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,232 control chromosomes in the GnomAD database, including 53,951 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 0.84 (53951 hom., cov: 34)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.82

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA8	NM_004056.6	c.292+6526A>G		intron_variant		ENST00000317995.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA8	ENST00000317995.5	c.292+6526A>G		intron_variant		1	NM_004056.6	P1
CA8	ENST00000524872.5	n.530+6526A>G		intron_variant, non_coding_transcript_variant		1
CA8	ENST00000529918.1	n.469+6526A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127916 AN: 152114 Hom.: 53902 Cov.: 34

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.833

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

GnomAD4 genome AF: 0.841 AC: 128025 AN: 152232 Hom.: 53951 Cov.: 34 AF XY: 0.842 AC XY: 62633 AN XY: 74428

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.811

Gnomad4 OTH AF: 0.835

Alfa AF: 0.813 Hom.: 74241

Bravo AF: 0.843

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.031
DANN	Benign	0.60

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: rs10216440; hg19: chr8-61185722;