chr8-85333004-A-G

Position:

• chr8-85333004-A-G

Variant summary

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

The NM_001128831.4(CA1):​c.451-452T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,074 control chromosomes in the GnomAD database, including 45,264 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 0.76 (45264 hom., cov: 32)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.419

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA1	NM_001128831.4	c.451-452T>C		intron_variant		ENST00000523022.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA1	ENST00000523022.6	c.451-452T>C		intron_variant		1	NM_001128831.4	P1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115739 AN: 151956 Hom.: 45203 Cov.: 32

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.762 AC: 115855 AN: 152074 Hom.: 45264 Cov.: 32 AF XY: 0.761 AC XY: 56539 AN XY: 74332

Gnomad4 AFR AF: 0.920

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.744

Alfa AF: 0.752 Hom.: 9891

Bravo AF: 0.751

Asia WGS AF: 0.582 AC: 2007 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.46

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: rs7011926; hg19: chr8-86245233;