rs10904850

chr10-16955708-G-A

Variant summary

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

The NM_001081.4(CUBN):c.4696-1160C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,956 control chromosomes in the GnomAD database, including 5,524 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 0.25 (5524 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.506

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.4696-1160C>T		intron_variant		ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.4696-1160C>T		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38120 AN: 151838 Hom.: 5513 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.251 AC: 38153 AN: 151956 Hom.: 5524 Cov.: 32 AF XY: 0.250 AC XY: 18585 AN XY: 74252

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.251

Alfa AF: 0.273 Hom.: 1009

Bravo AF: 0.232

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	6.4
Dann	Benign	0.65

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: rs10904850; hg19: chr10-16997707;