rs79801018

Variant names:

• chr10-16895660-T-C
• rs79801018
• NM_001081.4:c.8598+3336A>G

Variant summary

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

The NM_001081.4(CUBN):​c.8598+3336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,204 control chromosomes in the GnomAD database, including 839 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 0.10 (839 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• 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

ENSG00000296126 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8598+3336A>G		intron_variant	Intron 54 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4584+3336A>G		intron_variant	Intron 28 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.4560+3336A>G		intron_variant	Intron 28 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.4440+3336A>G		intron_variant	Intron 27 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8598+3336A>G		intron_variant	Intron 54 of 66	1	NM_001081.4	ENSP00000367064.4
ENSG00000296126	ENST00000736661.1	n.195+3026T>C		intron_variant	Intron 2 of 3
ENSG00000296126	ENST00000736662.1	n.100+4049T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15752 AN: 152086 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.104 AC: 15778 AN: 152204 Hom.: 839 Cov.: 32 AF XY: 0.101 AC XY: 7521 AN XY: 74436

African (AFR) AF: 0.123 AC: 5101 AN: 41510

American (AMR) AF: 0.0886 AC: 1355 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 519 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5188

South Asian (SAS) AF: 0.116 AC: 559 AN: 4832

European-Finnish (FIN) AF: 0.0783 AC: 830 AN: 10604

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7010 AN: 67996

Other (OTH) AF: 0.114 AC: 241 AN: 2110

Alfa AF: 0.101 Hom.: 248

Bravo AF: 0.105

Asia WGS AF: 0.0630 AC: 220 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.42
DANN	Benign	0.72
PhyloP100		-0.77
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: rs79801018; hg19: chr10-16937659;