rs10752067

Variant names:

• chr10-17106893-C-T
• rs10752067
• NM_001081.4:c.1112-1318G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

CUBN Gene-Disease associations (from GenCC):

• Imerslund-Grasbeck syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• proteinuria, chronic benign

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Imerslund-Grasbeck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081.4. 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
	CUBN	NM_001081.4	MANE Select	c.1112-1318G>A		intron	N/A	NP_001072.2	O60494

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	ENST00000377833.10	TSL:1 MANE Select	c.1112-1318G>A		intron	N/A	ENSP00000367064.4	O60494

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

African (AFR) AF: 0.670 AC: 27817 AN: 41496

American (AMR) AF: 0.885 AC: 13543 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3304 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4736 AN: 5172

South Asian (SAS) AF: 0.943 AC: 4555 AN: 4830

European-Finnish (FIN) AF: 0.946 AC: 10038 AN: 10614

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64914 AN: 68040

Other (OTH) AF: 0.882 AC: 1861 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-1.7
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: rs10752067; hg19: chr10-17148892;