rs45619139

chr10-16898847-C-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.8598+149G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 683,108 control chromosomes in the GnomAD database, including 3,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (547 hom., cov: 32)
  • Exomes 𝑓: 0.093 (2659 hom.)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.515

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=-0.85).
• BP6: Variant 10-16898847-C-G is Benign according to our data. Variant chr10-16898847-C-G is described in ClinVar as [Benign]. Clinvar id is 1294111.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8598+149G>C		intron_variant		ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8598+149G>C		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11850 AN: 152122 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.0761

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0801

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0933 AC: 49504 AN: 530868 Hom.: 2659 AF XY: 0.0950 AC XY: 27186 AN XY: 286084

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.0703

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.000713

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.0805

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.0778 AC: 11850 AN: 152240 Hom.: 547 Cov.: 32 AF XY: 0.0768 AC XY: 5715 AN XY: 74442

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0801

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.0920 Hom.: 93

Bravo AF: 0.0741

Asia WGS AF: 0.0570 AC: 200 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

Sep 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.45
Dann	Benign	0.61

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: rs45619139; hg19: chr10-16940846;