10-17086302-A-T

Position:

• chr10-17086302-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001081.4(CUBN):​c.1948-543T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.839 in 152,172 control chromosomes in the GnomAD database, including 53,628 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 0.84 (53628 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.1948-543T>A		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.1948-543T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.1948-543T>A		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127535 AN: 152054 Hom.: 53591 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.846

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.945

Gnomad SAS AF: 0.919

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.839 AC: 127630 AN: 152172 Hom.: 53628 Cov.: 31 AF XY: 0.844 AC XY: 62818 AN XY: 74398

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.945

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.862

Alfa AF: 0.828 Hom.: 6479

Bravo AF: 0.837

Asia WGS AF: 0.911 AC: 3168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.19
DANN	Benign	0.76

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: rs1543491; hg19: chr10-17128301;