8-85341067-C-T

Variant names:

• chr8-85341067-C-T
• rs2220972
• NM_001128831.4:c.37+532G>A

Variant summary

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

The NM_001128831.4(CA1):​c.37+532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 152,240 control chromosomes in the GnomAD database, including 25,941 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 0.58 (25869 hom., cov: 30)
  • Exomes 𝑓: 0.54 (72 hom.)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.37+532G>A		intron_variant	Intron 2 of 7	ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.37+532G>A		intron_variant	Intron 2 of 7	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88013 AN: 151640 Hom.: 25850 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.535 AC: 259 AN: 484 Hom.: 72 Cov.: 0 AF XY: 0.556 AC XY: 219 AN XY: 394

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.580 AC: 88064 AN: 151756 Hom.: 25869 Cov.: 30 AF XY: 0.582 AC XY: 43127 AN XY: 74158

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.595

Gnomad4 OTH AF: 0.607

Alfa AF: 0.586 Hom.: 3136

Bravo AF: 0.574

Asia WGS AF: 0.410 AC: 1425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.86

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: rs2220972; hg19: chr8-86253296;