8-60232231-G-T

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.513+53C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,366,382 control chromosomes in the GnomAD database, including 54,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7125 hom., cov: 32)
  • Exomes 𝑓: 0.27 (47423 hom.)
• Consequence: CA8 NM_004056.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.654

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=-0.84).
• BP6: Variant 8-60232231-G-T is Benign according to our data. Variant chr8-60232231-G-T is described in ClinVar as [Benign]. Clinvar id is 1267451.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA8	NM_004056.6	c.513+53C>A		intron_variant		ENST00000317995.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA8	ENST00000317995.5	c.513+53C>A		intron_variant		1	NM_004056.6	P1
CA8	ENST00000524872.5	n.751+53C>A		intron_variant, non_coding_transcript_variant		1
CA8	ENST00000528666.1	n.285+53C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45791 AN: 151898 Hom.: 7119 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.275 AC: 333595 AN: 1214366 Hom.: 47423 AF XY: 0.274 AC XY: 168924 AN XY: 616598

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.236

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.301 AC: 45819 AN: 152016 Hom.: 7125 Cov.: 32 AF XY: 0.299 AC XY: 22213 AN XY: 74288

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.312

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.324

Alfa AF: 0.284 Hom.: 921

Bravo AF: 0.312

Asia WGS AF: 0.275 AC: 953 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 19, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.4
Dann	Benign	0.65

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: rs73683396; hg19: chr8-61144790; COSMIC: COSV58772242;