rs17814594

Variant names:

• chr8-85342110-T-C
• rs17814594
• NM_001128831.4:c.-24-451A>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.-24-451A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,130 control chromosomes in the GnomAD database, including 1,374 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 0.12 (1374 hom., cov: 32)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.363
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.-24-451A>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.-24-451A>G		intron_variant	Intron 1 of 7	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18629 AN: 152012 Hom.: 1373 Cov.: 32

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.00731

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.123 AC: 18641 AN: 152130 Hom.: 1374 Cov.: 32 AF XY: 0.122 AC XY: 9055 AN XY: 74352

African (AFR) AF: 0.0593 AC: 2465 AN: 41546

American (AMR) AF: 0.0848 AC: 1295 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3472

East Asian (EAS) AF: 0.00733 AC: 38 AN: 5186

South Asian (SAS) AF: 0.155 AC: 749 AN: 4828

European-Finnish (FIN) AF: 0.160 AC: 1686 AN: 10550

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11635 AN: 67952

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.155 Hom.: 2968

Bravo AF: 0.110

Asia WGS AF: 0.0920 AC: 314 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.6
DANN	Benign	0.86
PhyloP100		-0.36
PromoterAI		-0.0027	Neutral
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: rs17814594; hg19: chr8-86254339;