rs10752067

Positions:

• chr10-17106893-C-T

Variant summary

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

The NM_001081.4(CUBN):​c.1112-1318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,236 control chromosomes in the GnomAD database, including 58,274 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 0.87 (58274 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

CUBN (HGNC:2548): (cubilin) Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.1112-1318G>A		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.1112-1318G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.1112-1318G>A		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131815 AN: 152118 Hom.: 58250 Cov.: 32

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.882

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

GnomAD4 genome AF: 0.866 AC: 131893 AN: 152236 Hom.: 58274 Cov.: 32 AF XY: 0.869 AC XY: 64699 AN XY: 74436

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.946

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.882

Alfa AF: 0.906 Hom.: 10643

Bravo AF: 0.849

Asia WGS AF: 0.914 AC: 3177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.54

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: rs10752067; hg19: chr10-17148892;