rs78936062

Positions:

• chr10-16885878-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.8905+2539T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 152,296 control chromosomes in the GnomAD database, including 575 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 0.083 (575 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.8905+2539T>A		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4891+2539T>A		intron_variant			XP_011518011.1
CUBN	XM_011519710.3	c.4867+2539T>A		intron_variant			XP_011518012.1
CUBN	XM_011519711.4	c.4747+2539T>A		intron_variant			XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8905+2539T>A		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.0826 AC: 12575 AN: 152178 Hom.: 574 Cov.: 33

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0780

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0961

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

GnomAD4 genome AF: 0.0825 AC: 12572 AN: 152296 Hom.: 575 Cov.: 33 AF XY: 0.0807 AC XY: 6011 AN XY: 74478

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0780

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0941

Alfa AF: 0.0942 Hom.: 102

Bravo AF: 0.0796

Asia WGS AF: 0.0600 AC: 210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.83

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: rs78936062; hg19: chr10-16927877;