rs2356216

Positions:

• chr10-17032579-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.4017+8454C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0606 in 152,208 control chromosomes in the GnomAD database, including 438 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 0.061 (438 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.672

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4017+8454C>G		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.4017+8454C>G		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4017+8454C>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.0605 AC: 9206 AN: 152088 Hom.: 437 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0610

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.0857

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0257

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0606 AC: 9219 AN: 152208 Hom.: 438 Cov.: 32 AF XY: 0.0639 AC XY: 4757 AN XY: 74410

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.0610

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0891

Gnomad4 FIN AF: 0.0857

Gnomad4 NFE AF: 0.0257

Gnomad4 OTH AF: 0.0491

Alfa AF: 0.0487 Hom.: 33

Bravo AF: 0.0610

Asia WGS AF: 0.127 AC: 441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
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: rs2356216; hg19: chr10-17074578;