10-16969176-A-G

Position:

• chr10-16969176-A-G

Variant summary

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

The NM_001081.4(CUBN):​c.4695+13308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,238 control chromosomes in the GnomAD database, including 56,432 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 0.86 (56432 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.4695+13308T>C		intron_variant		ENST00000377833.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.4695+13308T>C		intron_variant		1	NM_001081.4	P1
CUBN	ENST00000438254.1	n.262-3199T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130562 AN: 152120 Hom.: 56413 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.858 AC: 130633 AN: 152238 Hom.: 56432 Cov.: 33 AF XY: 0.856 AC XY: 63697 AN XY: 74434

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.869

Alfa AF: 0.894 Hom.: 102882

Bravo AF: 0.842

Asia WGS AF: 0.792 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.78
DANN	Benign	0.39

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: rs1398431; hg19: chr10-17011175;