10-16882610-G-C

Position:

• chr10-16882610-G-C

Variant summary

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

The NM_001081.4(CUBN):​c.8906-5513C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 152,258 control chromosomes in the GnomAD database, including 572 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 0.082 (572 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.607

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8906-5513C>G		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.4892-5513C>G		intron_variant
CUBN	XM_011519710.3	c.4868-5513C>G		intron_variant
CUBN	XM_011519711.4	c.4748-5513C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8906-5513C>G		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12501 AN: 152140 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.0821 AC: 12499 AN: 152258 Hom.: 572 Cov.: 33 AF XY: 0.0801 AC XY: 5965 AN XY: 74448

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0940

Alfa AF: 0.0410 Hom.: 37

Bravo AF: 0.0791

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.42

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: rs79051478; hg19: chr10-16924609;