10-17120315-T-C

Position:

• chr10-17120315-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.593+2480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,254 control chromosomes in the GnomAD database, including 63,779 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 0.91 (63779 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.593+2480A>G		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.593+2480A>G		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.593+2480A>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 139028 AN: 152136 Hom.: 63740 Cov.: 33

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.938

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.914 AC: 139124 AN: 152254 Hom.: 63779 Cov.: 33 AF XY: 0.914 AC XY: 68046 AN XY: 74444

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.904

Gnomad4 ASJ AF: 0.952

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.955

Gnomad4 OTH AF: 0.921

Alfa AF: 0.936 Hom.: 8298

Bravo AF: 0.904

Asia WGS AF: 0.924 AC: 3213 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.48

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: rs7078169; hg19: chr10-17162314;