8-85383194-C-T

Variant names:

• chr8-85383194-C-T
• rs13278559
• ENST00000520921.1:c.-239C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.73).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA3	ENST00000520921.1	c.-239C>T		5_prime_UTR_variant	Exon 2 of 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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0385 AC: 1 AN: 26

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0938 AC: 6 AN: 64

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.0211 AC: 876 AN: 41540

American (AMR) AF: 0.0521 AC: 797 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 245 AN: 3462

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5176

South Asian (SAS) AF: 0.0323 AC: 156 AN: 4828

European-Finnish (FIN) AF: 0.166 AC: 1764 AN: 10598

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6721 AN: 68002

Other (OTH) AF: 0.0730 AC: 154 AN: 2110

Alfa AF: 0.0805 Hom.: 1117

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
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs13278559; hg19: chr8-86295423;