rs74942409

Variant names:

• chr10-16886302-T-C
• rs74942409
• NM_001081.4:c.8905+2115A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-16886302-T-C
• chr10-16886302-T-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.8905+2115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 152,268 control chromosomes in the GnomAD database, including 563 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 0.080 (563 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8905+2115A>G		intron_variant	Intron 56 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4891+2115A>G		intron_variant	Intron 30 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.4867+2115A>G		intron_variant	Intron 30 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.4747+2115A>G		intron_variant	Intron 29 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8905+2115A>G		intron_variant	Intron 56 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0800 AC: 12173 AN: 152150 Hom.: 562 Cov.: 33

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0971

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

GnomAD4 genome AF: 0.0799 AC: 12171 AN: 152268 Hom.: 563 Cov.: 33 AF XY: 0.0781 AC XY: 5814 AN XY: 74446

African (AFR) AF: 0.0357 AC: 1483 AN: 41570

American (AMR) AF: 0.0802 AC: 1227 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 523 AN: 3468

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5182

South Asian (SAS) AF: 0.126 AC: 608 AN: 4828

European-Finnish (FIN) AF: 0.0783 AC: 830 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7144 AN: 68010

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0679 Hom.: 129

Bravo AF: 0.0764

Asia WGS AF: 0.0590 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.27
DANN	Benign	0.79
PhyloP100		-1.2
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: rs74942409; hg19: chr10-16928301;