rs17139663

chr10-17035418-A-Cchr10-17035418-A-T

Variant summary

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

The NM_001081.4(CUBN):c.4017+5615T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,206 control chromosomes in the GnomAD database, including 1,368 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 (1368 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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 (SAS) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.4017+5615T>G		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.4017+5615T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.4017+5615T>G		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18193 AN: 152088 Hom.: 1370 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0855

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.120 AC: 18206 AN: 152206 Hom.: 1368 Cov.: 32 AF XY: 0.126 AC XY: 9410 AN XY: 74402

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.0855

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0874 Hom.: 623

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.9
Dann	Benign	0.55

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: rs17139663; hg19: chr10-17077417;