10-16829322-T-G

Variant names:

• chr10-16829322-T-G
• rs11254232
• NM_001081.4:c.10529-282A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001081.4(CUBN):​c.10529-282A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 133,350 control chromosomes in the GnomAD database, including 949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (949 hom., cov: 29)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.537
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-16829322-T-G is Benign according to our data. Variant chr10-16829322-T-G is described in ClinVar as Benign. ClinVar VariationId is 1261577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.10529-282A>C		intron_variant	Intron 65 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.6515-282A>C		intron_variant	Intron 39 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.6491-282A>C		intron_variant	Intron 39 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.6371-282A>C		intron_variant	Intron 38 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.10529-282A>C		intron_variant	Intron 65 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 15633 AN: 133288 Hom.: 942 Cov.: 29

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0508

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.0385

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.117 AC: 15648 AN: 133350 Hom.: 949 Cov.: 29 AF XY: 0.122 AC XY: 7740 AN XY: 63654

African (AFR) AF: 0.175 AC: 6045 AN: 34466

American (AMR) AF: 0.0665 AC: 770 AN: 11572

Ashkenazi Jewish (ASJ) AF: 0.0508 AC: 170 AN: 3348

East Asian (EAS) AF: 0.181 AC: 743 AN: 4096

South Asian (SAS) AF: 0.151 AC: 626 AN: 4148

European-Finnish (FIN) AF: 0.182 AC: 1453 AN: 7972

Middle Eastern (MID) AF: 0.0369 AC: 9 AN: 244

European-Non Finnish (NFE) AF: 0.0852 AC: 5522 AN: 64812

Other (OTH) AF: 0.104 AC: 189 AN: 1824

Alfa AF: 0.0960 Hom.: 117

Bravo AF: 0.100

Asia WGS AF: 0.163 AC: 566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.33
PhyloP100		-0.54
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: rs11254232; hg19: chr10-16871321;