8-85331941-C-T

Variant names:

• chr8-85331941-C-T
• rs3808540
• NM_001128831.4:c.513+549G>A

Variant summary

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

The NM_001128831.4(CA1):​c.513+549G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.788 in 152,128 control chromosomes in the GnomAD database, including 48,194 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 0.79 (48194 hom., cov: 32)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.410
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CA1	NM_001128831.4	c.513+549G>A		intron_variant	Intron 6 of 7	ENST00000523022.6	NP_001122303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CA1	ENST00000523022.6	c.513+549G>A		intron_variant	Intron 6 of 7	1	NM_001128831.4	ENSP00000429798.1

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119833 AN: 152012 Hom.: 48135 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.788 AC: 119947 AN: 152128 Hom.: 48194 Cov.: 32 AF XY: 0.789 AC XY: 58626 AN XY: 74342

African (AFR) AF: 0.943 AC: 39179 AN: 41526

American (AMR) AF: 0.684 AC: 10429 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2483 AN: 3470

East Asian (EAS) AF: 0.614 AC: 3169 AN: 5162

South Asian (SAS) AF: 0.705 AC: 3397 AN: 4818

European-Finnish (FIN) AF: 0.836 AC: 8844 AN: 10580

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.736 AC: 50019 AN: 68002

Other (OTH) AF: 0.777 AC: 1642 AN: 2114

Alfa AF: 0.745 Hom.: 42685

Bravo AF: 0.781

Asia WGS AF: 0.699 AC: 2424 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.1
DANN	Benign	0.54
PhyloP100		0.41
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: rs3808540; hg19: chr8-86244170;