rs41289311

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001081.4(CUBN):c.1911C>T(p.Leu637Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 1,612,820 control chromosomes in the GnomAD database, including 2,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 204 hom., cov: 31)

Exomes 𝑓: 0.044 ( 2631 hom. )

Consequence

CUBN
NM_001081.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.343

Publications

9 publications found

Variant links:

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
proteinuria, chronic benign
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Imerslund-Grasbeck syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CUBN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-17088200-G-A is Benign according to our data. Variant chr10-17088200-G-A is described in ClinVar as Benign. ClinVar VariationId is 299519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.343 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4 link	c.1911C>T	p.Leu637Leu	synonymous_variant	Exon 15 of 67	ENST00000377833.10	NP_001072.2	O60494
CUBN	XM_011519708.3 link	c.1911C>T	p.Leu637Leu	synonymous_variant	Exon 15 of 55		XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10 link	c.1911C>T	p.Leu637Leu	synonymous_variant	Exon 15 of 67	1	NM_001081.4	ENSP00000367064.4		O60494

Frequencies

GnomAD3 genomes

AF:

0.0354

AC:

5371

AN:

151922

Hom.:

205

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0892

Gnomad EAS

AF:

0.0220

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.0521

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0347

Gnomad OTH

AF:

0.0388

GnomAD2 exomes

AF:

0.0536

AC:

13480

AN:

251284

AF XY:

0.0627

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0222

Gnomad ASJ exome

AF:

0.0857

Gnomad EAS exome

AF:

0.0205

Gnomad FIN exome

AF:

0.0478

Gnomad NFE exome

AF:

0.0377

Gnomad OTH exome

AF:

0.0501

GnomAD4 exome

AF:

0.0435

AC:

63583

AN:

1460780

Hom.:

2631

Cov.:

AF XY:

0.0484

AC XY:

35154

AN XY:

726762

show subpopulations

African (AFR)

AF:

0.0116

AC:

387

AN:

33478

American (AMR)

AF:

0.0232

AC:

1039

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0876

AC:

2289

AN:

26118

East Asian (EAS)

AF:

0.0195

AC:

775

AN:

39686

South Asian (SAS)

AF:

0.188

AC:

16227

AN:

86170

European-Finnish (FIN)

AF:

0.0470

AC:

2508

AN:

53416

Middle Eastern (MID)

AF:

0.0876

AC:

505

AN:

5766

European-Non Finnish (NFE)

AF:

0.0332

AC:

36854

AN:

1111094

Other (OTH)

AF:

0.0497

AC:

2999

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

2956

5912

8867

11823

14779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1472

2944

4416

5888

7360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0353

AC:

5367

AN:

152040

Hom.:

204

Cov.:

AF XY:

0.0389

AC XY:

2894

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0107

AC:

443

AN:

41480

American (AMR)

AF:

0.0272

AC:

415

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0892

AC:

309

AN:

3464

East Asian (EAS)

AF:

0.0221

AC:

114

AN:

5162

South Asian (SAS)

AF:

0.203

AC:

976

AN:

4798

European-Finnish (FIN)

AF:

0.0521

AC:

550

AN:

10562

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0347

AC:

2360

AN:

68002

Other (OTH)

AF:

0.0388

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

255

510

766

1021

1276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

228

304

380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0327

Hom.:

172

Bravo

AF:

0.0287

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

EpiCase

AF:

0.0451

EpiControl

AF:

0.0446

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Imerslund-Grasbeck syndrome type 1

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Imerslund-Grasbeck syndrome

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.1

(source)

DANN

Benign

0.62

PhyloP100

-0.34

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over