rs1810205

Variant names:

• chr10-16923228-A-G
• rs1810205
• NM_001081.4:c.6646+2013T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-16923228-A-G
• chr10-16923228-A-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.6646+2013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,780 control chromosomes in the GnomAD database, including 17,078 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 0.46 (17078 hom., cov: 30)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 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.6646+2013T>C		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.6646+2013T>C		intron	N/A	ENSP00000367064.4	O60494

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70251 AN: 151662 Hom.: 17060 Cov.: 30

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.463 AC: 70323 AN: 151780 Hom.: 17078 Cov.: 30 AF XY: 0.466 AC XY: 34545 AN XY: 74162

African (AFR) AF: 0.610 AC: 25242 AN: 41380

American (AMR) AF: 0.526 AC: 8005 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1258 AN: 3466

East Asian (EAS) AF: 0.441 AC: 2271 AN: 5146

South Asian (SAS) AF: 0.394 AC: 1885 AN: 4782

European-Finnish (FIN) AF: 0.435 AC: 4584 AN: 10542

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.377 AC: 25635 AN: 67936

Other (OTH) AF: 0.433 AC: 912 AN: 2106

Alfa AF: 0.405 Hom.: 21680

Bravo AF: 0.481

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.35
PhyloP100		2.2
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: rs1810205; hg19: chr10-16965227;