rs10904850

Variant names:

• chr10-16955708-G-A
• rs10904850
• NM_001081.4:c.4696-1160C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-16955708-G-A
• chr10-16955708-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.4696-1160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,956 control chromosomes in the GnomAD database, including 5,524 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 0.25 (5524 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506
• 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: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	NM_001081.4	MANE Select	c.4696-1160C>T		intron	N/A	NP_001072.2	O60494

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	ENST00000377833.10	TSL:1 MANE Select	c.4696-1160C>T		intron	N/A	ENSP00000367064.4	O60494

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38120 AN: 151838 Hom.: 5513 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.251 AC: 38153 AN: 151956 Hom.: 5524 Cov.: 32 AF XY: 0.250 AC XY: 18585 AN XY: 74252

African (AFR) AF: 0.117 AC: 4868 AN: 41462

American (AMR) AF: 0.195 AC: 2979 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3466

East Asian (EAS) AF: 0.156 AC: 806 AN: 5162

South Asian (SAS) AF: 0.263 AC: 1268 AN: 4814

European-Finnish (FIN) AF: 0.370 AC: 3887 AN: 10504

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.327 AC: 22220 AN: 67962

Other (OTH) AF: 0.251 AC: 530 AN: 2112

Alfa AF: 0.269 Hom.: 1016

Bravo AF: 0.232

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.4
DANN	Benign	0.65
PhyloP100		0.51
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: rs10904850; hg19: chr10-16997707;