rs11254313

Positions:

• chr10-16976281-T-C

Variant summary

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

The NM_001081.4(CUBN):​c.4695+6203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 151,928 control chromosomes in the GnomAD database, including 23,634 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 0.55 (23634 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4695+6203A>G		intron_variant		ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4695+6203A>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1
CUBN	ENST00000438254.1	n.261+6203A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83987 AN: 151806 Hom.: 23600 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.553 AC: 84077 AN: 151928 Hom.: 23634 Cov.: 31 AF XY: 0.550 AC XY: 40832 AN XY: 74232

Gnomad4 AFR AF: 0.590

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.525

Alfa AF: 0.562 Hom.: 3040

Bravo AF: 0.544

Asia WGS AF: 0.514 AC: 1788 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	2.3
DANN	Benign	0.54

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: rs11254313; hg19: chr10-17018280;