10-16895776-C-T

Position:

• chr10-16895776-C-T

Variant summary

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

The NM_001081.4(CUBN):​c.8598+3220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,048 control chromosomes in the GnomAD database, including 825 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 0.10 (825 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) 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.8598+3220G>A		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.4584+3220G>A		intron_variant			XP_011518011.1
CUBN	XM_011519710.3	c.4560+3220G>A		intron_variant			XP_011518012.1
CUBN	XM_011519711.4	c.4440+3220G>A		intron_variant			XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.8598+3220G>A		intron_variant		1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15646 AN: 151930 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.00174

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0788

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.103 AC: 15676 AN: 152048 Hom.: 825 Cov.: 32 AF XY: 0.100 AC XY: 7468 AN XY: 74318

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0788

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0466 Hom.: 47

Bravo AF: 0.104

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs78786782; hg19: chr10-16937775; COSMIC: COSV64713672;