rs12544332

Positions:

• chr8-85343981-C-A

Variant summary

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

The NM_001128831.4(CA1):​c.-24-2322G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 148,988 control chromosomes in the GnomAD database, including 24,712 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 0.57 (24712 hom., cov: 25)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

CA1 (HGNC:1368): (carbonic anhydrase 1) Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. This CA1 gene is closely linked to the CA2 and CA3 genes on chromosome 8. It encodes a cytosolic protein that is found at the highest level in erythrocytes. Allelic variants of this gene have been described in some populations. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CA1	NM_001128831.4	c.-24-2322G>T		intron_variant		ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.-24-2322G>T		intron_variant		1	NM_001128831.4	ENSP00000429798	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 85163 AN: 148900 Hom.: 24699 Cov.: 25

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.572 AC: 85196 AN: 148988 Hom.: 24712 Cov.: 25 AF XY: 0.573 AC XY: 41514 AN XY: 72506

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.599

Alfa AF: 0.594 Hom.: 5447

Bravo AF: 0.566

Asia WGS AF: 0.403 AC: 1394 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.014
DANN	Benign	0.52

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: rs12544332; hg19: chr8-86256210;