rs78625146

Variant names:

• chr10-16891840-T-A
• rs78625146
• NM_001081.4:c.8599-1313A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-16891840-T-A
• chr10-16891840-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001081.4(CUBN):​c.8599-1313A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,192 control chromosomes in the GnomAD database, including 541 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 0.078 (541 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222
• Publications: 3 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

ENSG00000296126 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8599-1313A>T		intron_variant	Intron 54 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4585-1313A>T		intron_variant	Intron 28 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.4561-1313A>T		intron_variant	Intron 28 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.4441-1313A>T		intron_variant	Intron 27 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8599-1313A>T		intron_variant	Intron 54 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11837 AN: 152074 Hom.: 540 Cov.: 31

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0914

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

GnomAD4 genome AF: 0.0778 AC: 11837 AN: 152192 Hom.: 541 Cov.: 31 AF XY: 0.0764 AC XY: 5685 AN XY: 74400

African (AFR) AF: 0.0313 AC: 1301 AN: 41512

American (AMR) AF: 0.0784 AC: 1198 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5180

South Asian (SAS) AF: 0.114 AC: 552 AN: 4824

European-Finnish (FIN) AF: 0.0792 AC: 839 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7089 AN: 68010

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0308 Hom.: 30

Bravo AF: 0.0741

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	3.4
DANN	Benign	0.78
PhyloP100		0.22
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: rs78625146; hg19: chr10-16933839;