rs10752062

Variant names:

• chr10-16864509-T-C
• rs10752062
• NM_001081.4:c.9454+5127A>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.9454+5127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,012 control chromosomes in the GnomAD database, including 20,438 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 (20438 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• 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: 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.9454+5127A>G		intron_variant	Intron 59 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.5440+5127A>G		intron_variant	Intron 33 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.5416+5127A>G		intron_variant	Intron 33 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.5296+5127A>G		intron_variant	Intron 32 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.9454+5127A>G		intron_variant	Intron 59 of 66	1	NM_001081.4	ENSP00000367064.4
CUBN	ENST00000649135.1	n.49+2298A>G		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70381 AN: 151894 Hom.: 20376 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.464 AC: 70509 AN: 152012 Hom.: 20438 Cov.: 31 AF XY: 0.467 AC XY: 34686 AN XY: 74294

African (AFR) AF: 0.812 AC: 33664 AN: 41480

American (AMR) AF: 0.479 AC: 7325 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1226 AN: 3472

East Asian (EAS) AF: 0.574 AC: 2970 AN: 5170

South Asian (SAS) AF: 0.414 AC: 1994 AN: 4814

European-Finnish (FIN) AF: 0.299 AC: 3154 AN: 10538

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.277 AC: 18850 AN: 67950

Other (OTH) AF: 0.443 AC: 932 AN: 2104

Alfa AF: 0.359 Hom.: 21827

Bravo AF: 0.497

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-1.7
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: rs10752062; hg19: chr10-16906508;