rs11254284

Positions:

• chr10-16936430-G-A
• chr10-16936430-G-C

Variant summary

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

The NM_001081.4(CUBN):​c.5926+1162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,048 control chromosomes in the GnomAD database, including 36,477 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 0.69 (36477 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.5926+1162C>T		intron_variant		ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.5926+1162C>T		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104542 AN: 151928 Hom.: 36412 Cov.: 32

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.688 AC: 104669 AN: 152048 Hom.: 36477 Cov.: 32 AF XY: 0.687 AC XY: 51031 AN XY: 74314

Gnomad4 AFR AF: 0.802

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.637

Alfa AF: 0.643 Hom.: 40503

Bravo AF: 0.699

Asia WGS AF: 0.641 AC: 2221 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.85
DANN	Benign	0.30

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: rs11254284; hg19: chr10-16978429; COSMIC: COSV64721014;