chr10-17035418-A-C

Variant names:

• chr10-17035418-A-C
• rs17139663
• NM_001081.4:c.4017+5615T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CUBN Gene-Disease associations (from GenCC):

• Imerslund-Grasbeck syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• proteinuria, chronic benign

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Imerslund-Grasbeck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4017+5615T>G		intron_variant	Intron 27 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.4017+5615T>G		intron_variant	Intron 27 of 54		XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4017+5615T>G		intron_variant	Intron 27 of 66	1	NM_001081.4	ENSP00000367064.4

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

African (AFR) AF: 0.125 AC: 5185 AN: 41532

American (AMR) AF: 0.108 AC: 1655 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1411 AN: 5152

South Asian (SAS) AF: 0.322 AC: 1553 AN: 4818

European-Finnish (FIN) AF: 0.171 AC: 1817 AN: 10610

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0855 AC: 5813 AN: 68006

Other (OTH) AF: 0.112 AC: 236 AN: 2116

Alfa AF: 0.0905 Hom.: 871

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
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17139663; hg19: chr10-17077417;