rs6602175

Variant names:

• chr10-17100527-G-T
• rs6602175
• NM_001081.4:c.1531-288C>A

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.1531-288C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 152,058 control chromosomes in the GnomAD database, including 29,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (29794 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 15 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=-0.98).
• BP6: Variant 10-17100527-G-T is Benign according to our data. Variant chr10-17100527-G-T is described in ClinVar as Benign. ClinVar VariationId is 1249861.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	NM_001081.4	MANE Select	c.1531-288C>A		intron	N/A	NP_001072.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUBN	ENST00000377833.10	TSL:1 MANE Select	c.1531-288C>A		intron	N/A	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92666 AN: 151940 Hom.: 29775 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.610 AC: 92721 AN: 152058 Hom.: 29794 Cov.: 33 AF XY: 0.607 AC XY: 45124 AN XY: 74340

African (AFR) AF: 0.403 AC: 16702 AN: 41450

American (AMR) AF: 0.641 AC: 9792 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1950 AN: 3466

East Asian (EAS) AF: 0.671 AC: 3469 AN: 5172

South Asian (SAS) AF: 0.567 AC: 2732 AN: 4818

European-Finnish (FIN) AF: 0.619 AC: 6539 AN: 10562

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49512 AN: 67988

Other (OTH) AF: 0.598 AC: 1263 AN: 2112

Alfa AF: 0.678 Hom.: 83369

Bravo AF: 0.601

Asia WGS AF: 0.620 AC: 2152 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.22
DANN	Benign	0.22
PhyloP100		-1.1
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: rs6602175; hg19: chr10-17142526;