rs11254284

Variant names:

• chr10-16936430-G-A
• rs11254284
• NM_001081.4:c.5926+1162C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-16936430-G-A
• chr10-16936430-G-C

Variant summary

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

The NM_001081.4(CUBN):​c.5926+1162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,048 control chromosomes in the GnomAD database, including 36,477 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 0.69 (36477 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.5926+1162C>T		intron_variant	Intron 39 of 66	ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.5926+1162C>T		intron_variant	Intron 39 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104542 AN: 151928 Hom.: 36412 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.688 AC: 104669 AN: 152048 Hom.: 36477 Cov.: 32 AF XY: 0.687 AC XY: 51031 AN XY: 74314

African (AFR) AF: 0.802 AC: 33264 AN: 41496

American (AMR) AF: 0.650 AC: 9933 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2001 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3539 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2911 AN: 4818

European-Finnish (FIN) AF: 0.678 AC: 7150 AN: 10544

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.644 AC: 43786 AN: 67964

Other (OTH) AF: 0.637 AC: 1343 AN: 2108

Alfa AF: 0.650 Hom.: 52490

Bravo AF: 0.699

Asia WGS AF: 0.641 AC: 2221 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.30
PhyloP100		0.30
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: rs11254284; hg19: chr10-16978429; COSMIC: COSV64721014;