rs6602175

Positions:

• chr10-17100527-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.1531-288C>A		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.1531-288C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.1531-288C>A		intron_variant		1	NM_001081.4	P1

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

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.567

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.598

Alfa AF: 0.703 Hom.: 56357

Bravo AF: 0.601

Asia WGS AF: 0.620 AC: 2152 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.22
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs6602175; hg19: chr10-17142526;