Variant rs7070148 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001081.4(CUBN):c.593+169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 653,454 control chromosomes in the GnomAD database, including 3,576 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 512 hom., cov: 32)

Exomes 𝑓: 0.095 ( 3064 hom. )

Consequence

CUBN
NM_001081.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.180

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-17122626-A-C is Benign according to our data. Variant chr10-17122626-A-C is described in ClinVar as [Benign]. Clinvar id is 1286315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4 linkuse as main transcript	c.593+169T>G		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3 linkuse as main transcript	c.593+169T>G		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10 linkuse as main transcript	c.593+169T>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1
CUBN	ENST00000433666.5 linkuse as main transcript	c.255-41T>G		intron_variant		5		ENSP00000415970

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10177

AN:

152126

Hom.:

513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.0476

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.0242

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0907

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0831

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0916

AC:

10693

AN:

116756

Hom.:

704

AF XY:

0.101

AC XY:

6306

AN XY:

62516

show subpopulations

Gnomad AFR exome

AF:

0.0170

Gnomad AMR exome

AF:

0.0423

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.0213

Gnomad SAS exome

AF:

0.224

Gnomad FIN exome

AF:

0.0890

Gnomad NFE exome

AF:

0.0878

Gnomad OTH exome

AF:

0.0806

GnomAD4 exome

AF:

0.0947

AC:

47489

AN:

501210

Hom.:

3064

Cov.:

AF XY:

0.103

AC XY:

28172

AN XY:

272392

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.0416

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.0207

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0890

Gnomad4 NFE exome

AF:

0.0862

Gnomad4 OTH exome

AF:

0.0860

GnomAD4 genome

AF:

0.0668

AC:

10174

AN:

152244

Hom.:

512

Cov.:

AF XY:

0.0703

AC XY:

5230

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.0476

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.0243

Gnomad4 SAS

AF:

0.239

Gnomad4 FIN

AF:

0.0907

Gnomad4 NFE

AF:

0.0831

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.0817

Hom.:

402

Bravo

AF:

0.0569

Asia WGS

AF:

0.104

AC:

362

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.0

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over