8-85360326-T-C

Variant names:

• chr8-85360326-T-C
• rs2645049
• NM_001128831.4:c.-25+17720A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128831.4(CA1):​c.-25+17720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,236 control chromosomes in the GnomAD database, including 49,155 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 (49155 hom., cov: 33)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 2 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.-25+17720A>G		intron_variant	Intron 1 of 7	ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.-25+17720A>G		intron_variant	Intron 1 of 7	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120973 AN: 152118 Hom.: 49099 Cov.: 33

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.854

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.795 AC: 121086 AN: 152236 Hom.: 49155 Cov.: 33 AF XY: 0.794 AC XY: 59106 AN XY: 74442

African (AFR) AF: 0.935 AC: 38837 AN: 41554

American (AMR) AF: 0.669 AC: 10225 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2493 AN: 3472

East Asian (EAS) AF: 0.496 AC: 2567 AN: 5176

South Asian (SAS) AF: 0.698 AC: 3370 AN: 4826

European-Finnish (FIN) AF: 0.854 AC: 9058 AN: 10606

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.765 AC: 52039 AN: 68008

Other (OTH) AF: 0.798 AC: 1683 AN: 2108

Alfa AF: 0.805 Hom.: 7536

Bravo AF: 0.787

Asia WGS AF: 0.641 AC: 2230 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.095
DANN	Benign	0.48
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2645049; hg19: chr8-86272555;