rs11254375

Positions:

• chr10-17117193-T-G

Variant summary

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

The NM_001081.4(CUBN):​c.594-1596A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,440 control chromosomes in the GnomAD database, including 6,769 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 0.29 (6769 hom., cov: 29)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.594-1596A>C		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.594-1596A>C		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.594-1596A>C		intron_variant		1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44197 AN: 151322 Hom.: 6764 Cov.: 29

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.292 AC: 44222 AN: 151440 Hom.: 6769 Cov.: 29 AF XY: 0.283 AC XY: 20902 AN XY: 73954

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.235

Alfa AF: 0.301 Hom.: 10847

Bravo AF: 0.288

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.72

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: rs11254375; hg19: chr10-17159192;