8-60227104-C-A

Position:

• chr8-60227104-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004056.6(CA8):​c.514-169G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 152,240 control chromosomes in the GnomAD database, including 65,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.93 (65909 hom., cov: 31)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 8-60227104-C-A is Benign according to our data. Variant chr8-60227104-C-A is described in ClinVar as [Benign]. Clinvar id is 1228305.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA8	NM_004056.6	c.514-169G>T		intron_variant		ENST00000317995.5	NP_004047.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA8	ENST00000317995.5	c.514-169G>T		intron_variant		1	NM_004056.6	ENSP00000314407	P1
CA8	ENST00000524872.5	n.752-169G>T		intron_variant, non_coding_transcript_variant		1
CA8	ENST00000528666.1	n.286-169G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.929 AC: 141345 AN: 152122 Hom.: 65851 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.929 AC: 141464 AN: 152240 Hom.: 65909 Cov.: 31 AF XY: 0.924 AC XY: 68762 AN XY: 74420

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.936

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.933

Gnomad4 OTH AF: 0.932

Alfa AF: 0.935 Hom.: 8271

Bravo AF: 0.935

Asia WGS AF: 0.816 AC: 2841 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.27

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: rs4738799; hg19: chr8-61139663;