rs2548281

Variant names:

• chr8-85398547-A-G
• rs2548281
• ENST00000520921.1:c.-198+15312A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520921.1(CA3):​c.-198+15312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,156 control chromosomes in the GnomAD database, including 37,749 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 0.69 (37749 hom., cov: 32)
• Consequence: CA3 ENST00000520921.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 4 publications found

Genes affected

CA3 (HGNC:1374): (carbonic anhydrase 3) Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns. [provided by RefSeq, Oct 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA3	ENST00000520921.1	c.-198+15312A>G		intron_variant	Intron 2 of 3	4		ENSP00000429760.1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105501 AN: 152036 Hom.: 37701 Cov.: 32

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.733

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.694 AC: 105605 AN: 152156 Hom.: 37749 Cov.: 32 AF XY: 0.692 AC XY: 51461 AN XY: 74392

African (AFR) AF: 0.861 AC: 35765 AN: 41538

American (AMR) AF: 0.604 AC: 9229 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2135 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2546 AN: 5164

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.733 AC: 7762 AN: 10584

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43350 AN: 67984

Other (OTH) AF: 0.716 AC: 1515 AN: 2116

Alfa AF: 0.647 Hom.: 16538

Bravo AF: 0.695

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2548281; hg19: chr8-86310776;