rs34456327

Variant names:

• chr8-85333263-T-TG
• rs34456327
• NM_001128831.4:c.450+261dupC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001128831.4(CA1):​c.450+261dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.716
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA1	NM_001128831.4	MANE Select	c.450+261dupC		intron	N/A	NP_001122303.1	P00915
	CA1	NM_001128829.4		c.450+261dupC		intron	N/A	NP_001122301.1	P00915
	CA1	NM_001128830.4		c.450+261dupC		intron	N/A	NP_001122302.1	P00915

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA1	ENST00000523022.6	TSL:1 MANE Select	c.450+261_450+262insC		intron	N/A	ENSP00000429798.1	P00915
	CA1	ENST00000523953.5	TSL:1	c.450+261_450+262insC		intron	N/A	ENSP00000430656.1	P00915
	CA1	ENST00000517618.5	TSL:1	c.450+261_450+262insC		intron	N/A	ENSP00000430861.1	E5RHP7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34456327;

hg19: chr8-86245492;