rs11254313

Variant names:

• chr10-16976281-T-C
• rs11254313
• NM_001081.4:c.4695+6203A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081.4(CUBN):​c.4695+6203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,928 control chromosomes in the GnomAD database, including 23,634 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 0.55 (23634 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 1 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: 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

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 (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4695+6203A>G		intron_variant	Intron 31 of 66	ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4695+6203A>G		intron_variant	Intron 31 of 66	1	NM_001081.4	ENSP00000367064.4
CUBN	ENST00000438254.1	n.261+6203A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83987 AN: 151806 Hom.: 23600 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.553 AC: 84077 AN: 151928 Hom.: 23634 Cov.: 31 AF XY: 0.550 AC XY: 40832 AN XY: 74232

African (AFR) AF: 0.590 AC: 24452 AN: 41428

American (AMR) AF: 0.427 AC: 6526 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1618 AN: 3462

East Asian (EAS) AF: 0.472 AC: 2435 AN: 5164

South Asian (SAS) AF: 0.505 AC: 2430 AN: 4810

European-Finnish (FIN) AF: 0.612 AC: 6438 AN: 10528

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38355 AN: 67954

Other (OTH) AF: 0.525 AC: 1108 AN: 2112

Alfa AF: 0.563 Hom.: 3177

Bravo AF: 0.544

Asia WGS AF: 0.514 AC: 1788 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	2.3
DANN	Benign	0.54
PhyloP100		-0.37
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: rs11254313; hg19: chr10-17018280;