10-16999474-T-G

Position:

• chr10-16999474-T-G

Variant summary

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

The ENST00000377833.10(CUBN):​c.4169-8959A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,174 control chromosomes in the GnomAD database, including 5,824 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 0.26 (5824 hom., cov: 33)
• Consequence: CUBN ENST00000377833.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4169-8959A>C		intron_variant		ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4169-8959A>C		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39388 AN: 152056 Hom.: 5820 Cov.: 33

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.259 AC: 39411 AN: 152174 Hom.: 5824 Cov.: 33 AF XY: 0.262 AC XY: 19497 AN XY: 74406

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.259

Alfa AF: 0.272 Hom.: 3304

Bravo AF: 0.256

Asia WGS AF: 0.314 AC: 1091 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.75

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: rs10508518; hg19: chr10-17041473;