rs10508517

Positions:

• chr10-16955892-G-A
• chr10-16955892-G-C
• chr10-16955892-G-T

Variant summary

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

The NM_001081.4(CUBN):​c.4696-1344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,140 control chromosomes in the GnomAD database, including 1,154 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 0.085 (1154 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.4696-1344C>T		intron_variant		ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.4696-1344C>T		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12917 AN: 152022 Hom.: 1150 Cov.: 33

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0850 AC: 12936 AN: 152140 Hom.: 1154 Cov.: 33 AF XY: 0.0930 AC XY: 6919 AN XY: 74372

Gnomad4 AFR AF: 0.0603

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.0893

Gnomad4 NFE AF: 0.0403

Gnomad4 OTH AF: 0.0806

Alfa AF: 0.0582 Hom.: 1355

Bravo AF: 0.0968

Asia WGS AF: 0.250 AC: 867 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.53

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: rs10508517; hg19: chr10-16997891;