rs13276893

chr8-85338718-T-C

Variant summary

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

The NM_001128831.4(CA1):c.38-269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 (18309 hom., cov: 20)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CA1	NM_001128831.4	c.38-269A>G		intron_variant		ENST00000523022.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CA1	ENST00000523022.6	c.38-269A>G		intron_variant		1	NM_001128831.4	P1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 69210 AN: 122444 Hom.: 18308 Cov.: 20

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.536

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.565 AC: 69206 AN: 122442 Hom.: 18309 Cov.: 20 AF XY: 0.565 AC XY: 32990 AN XY: 58374

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.574

Alfa AF: 0.508 Hom.: 1500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.1
Dann	Benign	0.35

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: rs13276893; hg19: chr8-86250947;