rs78625146

Positions:

• chr10-16891840-T-A
• chr10-16891840-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001081.4(CUBN):​c.8599-1313A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 152,192 control chromosomes in the GnomAD database, including 541 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 0.078 (541 hom., cov: 31)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.222

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8599-1313A>T		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.4585-1313A>T		intron_variant
CUBN	XM_011519710.3	c.4561-1313A>T		intron_variant
CUBN	XM_011519711.4	c.4441-1313A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8599-1313A>T		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11837 AN: 152074 Hom.: 540 Cov.: 31

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.0914

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

GnomAD4 genome AF: 0.0778 AC: 11837 AN: 152192 Hom.: 541 Cov.: 31 AF XY: 0.0764 AC XY: 5685 AN XY: 74400

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0784

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.0895

Alfa AF: 0.0308 Hom.: 30

Bravo AF: 0.0741

Asia WGS AF: 0.0560 AC: 197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	3.4
DANN	Benign	0.78

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: rs78625146; hg19: chr10-16933839;