10-17116291-C-G

Position:

• chr10-17116291-C-G

Variant summary

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

The NM_001081.4(CUBN):​c.594-694G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,158 control chromosomes in the GnomAD database, including 20,068 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 0.51 (20068 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.594-694G>C		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.594-694G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.594-694G>C		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77041 AN: 152040 Hom.: 20048 Cov.: 33

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.566

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.507 AC: 77104 AN: 152158 Hom.: 20068 Cov.: 33 AF XY: 0.509 AC XY: 37870 AN XY: 74374

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.508

Alfa AF: 0.372 Hom.: 931

Bravo AF: 0.505

Asia WGS AF: 0.603 AC: 2095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.34
DANN	Benign	0.51

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: rs7899751; hg19: chr10-17158290;