chr10-17091684-T-C

Position:

• chr10-17091684-T-C

Variant summary

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

The NM_001081.4(CUBN):​c.1766-3339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,104 control chromosomes in the GnomAD database, including 10,191 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 0.33 (10191 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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 (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.1766-3339A>G		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.1766-3339A>G		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.1766-3339A>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50462 AN: 151986 Hom.: 10175 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.419

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.332 AC: 50486 AN: 152104 Hom.: 10191 Cov.: 32 AF XY: 0.338 AC XY: 25111 AN XY: 74356

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.419

Gnomad4 OTH AF: 0.373

Alfa AF: 0.411 Hom.: 17569

Bravo AF: 0.329

Asia WGS AF: 0.450 AC: 1560 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.50

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: rs1996316; hg19: chr10-17133683;