10-16869116-C-T

Variant summary

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

The NM_001081.4(CUBN):c.9454+520G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,316 control chromosomes in the GnomAD database, including 1,356 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 0.12 (1356 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.9454+520G>A		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.5440+520G>A		intron_variant
CUBN	XM_011519710.3	c.5416+520G>A		intron_variant
CUBN	XM_011519711.4	c.5296+520G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.9454+520G>A		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17544 AN: 151248 Hom.: 1358 Cov.: 31

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.116 AC: 17537 AN: 151316 Hom.: 1356 Cov.: 31 AF XY: 0.112 AC XY: 8270 AN XY: 73878

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00137

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.130

Alfa AF: 0.145 Hom.: 1170

Bravo AF: 0.112

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.34
Dann	Benign	0.74

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: rs11591606; hg19: chr10-16911115;