Variant 8-60227048-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004056.6(CA8):c.514-113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 770,548 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.016 ( 73 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 35 hom. )

Consequence

CA8
NM_004056.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.892

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-60227048-T-C is Benign according to our data. Variant chr8-60227048-T-C is described in ClinVar as [Benign]. Clinvar id is 1266112.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA8	NM_004056.6 linkuse as main transcript	c.514-113A>G		intron_variant		ENST00000317995.5

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CA8	ENST00000317995.5 linkuse as main transcript	c.514-113A>G	intron_variant	1	NM_004056.6	P1
CA8	ENST00000524872.5 linkuse as main transcript	n.752-113A>G	intron_variant, non_coding_transcript_variant	1
CA8	ENST00000528666.1 linkuse as main transcript	n.286-113A>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2413

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00564

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00864

GnomAD4 exome

AF:

0.00187

AC:

1159

AN:

618428

Hom.:

AF XY:

0.00146

AC XY:

488

AN XY:

334174

show subpopulations

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.00269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000759

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000695

Gnomad4 OTH exome

AF:

0.00352

GnomAD4 genome

AF:

0.0159

AC:

2415

AN:

152120

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1177

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0554

Gnomad4 AMR

AF:

0.00563

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00855

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0177

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

4.7

Dann

Benign

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over