rs1496529

chr8-85347872-G-Achr8-85347872-G-T

Variant summary

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

The NM_001128831.4(CA1):c.-24-6213C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,096 control chromosomes in the GnomAD database, including 49,670 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 0.80 (49670 hom., cov: 31)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA1	NM_001128831.4	c.-24-6213C>T		intron_variant		ENST00000523022.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA1	ENST00000523022.6	c.-24-6213C>T		intron_variant		1	NM_001128831.4	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121527 AN: 151978 Hom.: 49611 Cov.: 31

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.799

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

GnomAD4 genome AF: 0.800 AC: 121642 AN: 152096 Hom.: 49670 Cov.: 31 AF XY: 0.797 AC XY: 59272 AN XY: 74358

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.780

Gnomad4 OTH AF: 0.801

Alfa AF: 0.804 Hom.: 5909

Bravo AF: 0.791

Asia WGS AF: 0.591 AC: 2052 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.85
Dann	Benign	0.67

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: rs1496529; hg19: chr8-86260101;