rs780846

chr10-16889011-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081.4(CUBN):c.8756-445G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,106 control chromosomes in the GnomAD database, including 44,166 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 0.76 (44166 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8756-445G>T		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.4742-445G>T		intron_variant
CUBN	XM_011519710.3	c.4718-445G>T		intron_variant
CUBN	XM_011519711.4	c.4598-445G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8756-445G>T		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114840 AN: 151988 Hom.: 44139 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.755 AC: 114909 AN: 152106 Hom.: 44166 Cov.: 33 AF XY: 0.746 AC XY: 55468 AN XY: 74354

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.615

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.520

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.663

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.753

Alfa AF: 0.729 Hom.: 6483

Bravo AF: 0.752

Asia WGS AF: 0.627 AC: 2181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.016
Dann	Benign	0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs780846; hg19: chr10-16931010;