rs780846

Variant names:

• chr10-16889011-C-A
• rs780846
• NM_001081.4:c.8756-445G>T

Variant summary

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

The NM_001081.4(CUBN):​c.8756-445G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,106 control chromosomes in the GnomAD database, including 44,166 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 0.76 (44166 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• 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: 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8756-445G>T		intron_variant	Intron 55 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4742-445G>T		intron_variant	Intron 29 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.4718-445G>T		intron_variant	Intron 29 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.4598-445G>T		intron_variant	Intron 28 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8756-445G>T		intron_variant	Intron 55 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114840 AN: 151988 Hom.: 44139 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.755 AC: 114909 AN: 152106 Hom.: 44166 Cov.: 33 AF XY: 0.746 AC XY: 55468 AN XY: 74354

African (AFR) AF: 0.866 AC: 35930 AN: 41510

American (AMR) AF: 0.615 AC: 9397 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2845 AN: 3470

East Asian (EAS) AF: 0.520 AC: 2684 AN: 5166

South Asian (SAS) AF: 0.697 AC: 3363 AN: 4824

European-Finnish (FIN) AF: 0.663 AC: 7000 AN: 10566

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51195 AN: 67972

Other (OTH) AF: 0.753 AC: 1591 AN: 2112

Alfa AF: 0.733 Hom.: 6769

Bravo AF: 0.752

Asia WGS AF: 0.627 AC: 2181 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	0.016
DANN	Benign	0.21
PhyloP100		-2.4
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: rs780846; hg19: chr10-16931010;