chr8-85383194-C-T

Position:

• chr8-85383194-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520921.1(CA3):​c.-239C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,310 control chromosomes in the GnomAD database, including 564 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 0.071 (563 hom., cov: 32)
  • Exomes 𝑓: 0.077 (1 hom.)
• Consequence: CA3 ENST00000520921.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA3	ENST00000520921.1	c.-239C>T		5_prime_UTR_variant	2/4	4		ENSP00000429760.1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10802 AN: 152088 Hom.: 563 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0708

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.0738

GnomAD4 exome AF: 0.0769 AC: 8 AN: 104 Hom.: 1 Cov.: 0 AF XY: 0.0735 AC XY: 5 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0710 AC: 10803 AN: 152206 Hom.: 563 Cov.: 32 AF XY: 0.0728 AC XY: 5420 AN XY: 74426

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0708

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0323

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0869 Hom.: 855

Bravo AF: 0.0622

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.8
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13278559; hg19: chr8-86295423;