10-16882610-G-C

Variant names:

• chr10-16882610-G-C
• rs79051478
• NM_001081.4:c.8906-5513C>G

Variant summary

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

The ENST00000377833.10(CUBN):​c.8906-5513C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 152,258 control chromosomes in the GnomAD database, including 572 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 0.082 (572 hom., cov: 33)
• Consequence: CUBN ENST00000377833.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377833.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	NM_001081.4	MANE Select	c.8906-5513C>G		intron	N/A	NP_001072.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	ENST00000377833.10	TSL:1 MANE Select	c.8906-5513C>G		intron	N/A	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12501 AN: 152140 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.0821 AC: 12499 AN: 152258 Hom.: 572 Cov.: 33 AF XY: 0.0801 AC XY: 5965 AN XY: 74448

African (AFR) AF: 0.0430 AC: 1785 AN: 41542

American (AMR) AF: 0.0808 AC: 1236 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 522 AN: 3466

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.125 AC: 605 AN: 4826

European-Finnish (FIN) AF: 0.0788 AC: 837 AN: 10618

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7160 AN: 68006

Other (OTH) AF: 0.0940 AC: 199 AN: 2116

Alfa AF: 0.0410 Hom.: 37

Bravo AF: 0.0791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-0.61
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: rs79051478; hg19: chr10-16924609;