10-17104668-C-T

Position:

• chr10-17104668-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001081.4(CUBN):​c.1231-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.949 in 1,100,476 control chromosomes in the GnomAD database, including 495,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (67429 hom., cov: 27)
  • Exomes 𝑓: 0.95 (428168 hom.)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.399

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-17104668-C-T is Benign according to our data. Variant chr10-17104668-C-T is described in ClinVar as [Benign]. Clinvar id is 1259729.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.1231-63G>A		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.1231-63G>A		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.1231-63G>A		intron_variant		1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.951 AC: 141734 AN: 149002 Hom.: 67421 Cov.: 27

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.954

Gnomad NFE AF: 0.956

Gnomad OTH AF: 0.951

GnomAD4 exome AF: 0.949 AC: 902469 AN: 951452 Hom.: 428168 AF XY: 0.949 AC XY: 464558 AN XY: 489690

Gnomad4 AFR exome AF: 0.960

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.946

Gnomad4 EAS exome AF: 0.928

Gnomad4 SAS exome AF: 0.946

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.951

Gnomad4 OTH exome AF: 0.949

GnomAD4 genome AF: 0.951 AC: 141752 AN: 149024 Hom.: 67429 Cov.: 27 AF XY: 0.950 AC XY: 68999 AN XY: 72598

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.923

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.956

Gnomad4 OTH AF: 0.950

Alfa AF: 0.956 Hom.: 8133

Bravo AF: 0.949

Asia WGS AF: 0.929 AC: 3232 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.5
DANN	Benign	0.31

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: rs4748353; hg19: chr10-17146667;