chr8-85338718-T-C

Variant names:

• chr8-85338718-T-C
• rs13276893
• NM_001128831.4:c.38-269A>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.38-269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.57 (18309 hom., cov: 20)
• Consequence: CA1 NM_001128831.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128831.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA1	NM_001128831.4	MANE Select	c.38-269A>G		intron	N/A	NP_001122303.1	P00915
	CA1	NM_001128829.4		c.38-269A>G		intron	N/A	NP_001122301.1	P00915
	CA1	NM_001128830.4		c.38-269A>G		intron	N/A	NP_001122302.1	P00915

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CA1	ENST00000523022.6	TSL:1 MANE Select	c.38-269A>G		intron	N/A	ENSP00000429798.1	P00915
	CA1	ENST00000523953.5	TSL:1	c.38-269A>G		intron	N/A	ENSP00000430656.1	P00915
	CA1	ENST00000517618.5	TSL:1	c.38-269A>G		intron	N/A	ENSP00000430861.1	E5RHP7

Frequencies

GnomAD3 genomes AF: 0.565 AC: 69210 AN: 122444 Hom.: 18308 Cov.: 20

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.536

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.565 AC: 69206 AN: 122442 Hom.: 18309 Cov.: 20 AF XY: 0.565 AC XY: 32990 AN XY: 58374

African (AFR) AF: 0.642 AC: 18186 AN: 28308

American (AMR) AF: 0.526 AC: 6129 AN: 11660

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1790 AN: 3260

East Asian (EAS) AF: 0.474 AC: 1811 AN: 3824

South Asian (SAS) AF: 0.465 AC: 1877 AN: 4034

European-Finnish (FIN) AF: 0.650 AC: 3847 AN: 5914

Middle Eastern (MID) AF: 0.543 AC: 138 AN: 254

European-Non Finnish (NFE) AF: 0.543 AC: 34000 AN: 62582

Other (OTH) AF: 0.574 AC: 995 AN: 1732

Alfa AF: 0.508 Hom.: 1500

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-0.23
PromoterAI		0.0085	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: rs13276893; hg19: chr8-86250947;