8-85356084-A-G

Variant names:

• chr8-85356084-A-G
• rs1532423
• NM_001128831.4:c.-24-14425T>C

Variant summary

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

The NM_001128831.4(CA1):​c.-24-14425T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 152,028 control chromosomes in the GnomAD database, including 33,175 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 0.65 (33175 hom., cov: 32)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 32 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.-24-14425T>C		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.-24-14425T>C		intron_variant	Intron 1 of 7	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98648 AN: 151910 Hom.: 33136 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.649 AC: 98740 AN: 152028 Hom.: 33175 Cov.: 32 AF XY: 0.649 AC XY: 48200 AN XY: 74302

African (AFR) AF: 0.817 AC: 33892 AN: 41494

American (AMR) AF: 0.570 AC: 8699 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2053 AN: 3472

East Asian (EAS) AF: 0.443 AC: 2285 AN: 5160

South Asian (SAS) AF: 0.502 AC: 2420 AN: 4822

European-Finnish (FIN) AF: 0.693 AC: 7311 AN: 10548

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39985 AN: 67960

Other (OTH) AF: 0.669 AC: 1412 AN: 2112

Alfa AF: 0.604 Hom.: 88292

Bravo AF: 0.652

Asia WGS AF: 0.484 AC: 1685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.4
DANN	Benign	0.76
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1532423; hg19: chr8-86268313;