rs11254232

Positions:

• chr10-16829322-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001081.4(CUBN):​c.10529-282A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 133,350 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (949 hom., cov: 29)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.537

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-16829322-T-G is Benign according to our data. Variant chr10-16829322-T-G is described in ClinVar as [Benign]. Clinvar id is 1261577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.10529-282A>C		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.6515-282A>C		intron_variant
CUBN	XM_011519710.3	c.6491-282A>C		intron_variant
CUBN	XM_011519711.4	c.6371-282A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.10529-282A>C		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 15633 AN: 133288 Hom.: 942 Cov.: 29

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.117 AC: 15648 AN: 133350 Hom.: 949 Cov.: 29 AF XY: 0.122 AC XY: 7740 AN XY: 63654

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.0665

Gnomad4 ASJ AF: 0.0508

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0951 Hom.: 109

Bravo AF: 0.100

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.33

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: rs11254232; hg19: chr10-16871321;