rs10904831

chr10-16889345-C-T

Variant summary

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

The NM_001081.4(CUBN):c.8756-779G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.08 in 152,202 control chromosomes in the GnomAD database, including 969 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 0.080 (969 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8756-779G>A		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.4742-779G>A		intron_variant
CUBN	XM_011519710.3	c.4718-779G>A		intron_variant
CUBN	XM_011519711.4	c.4598-779G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8756-779G>A		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12141 AN: 152084 Hom.: 955 Cov.: 32

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0800 AC: 12183 AN: 152202 Hom.: 969 Cov.: 32 AF XY: 0.0886 AC XY: 6591 AN XY: 74406

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0947

Alfa AF: 0.0777 Hom.: 395

Bravo AF: 0.0876

Asia WGS AF: 0.244 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.81
Dann	Benign	0.23

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: rs10904831; hg19: chr10-16931344;