rs1276721

Positions:

• chr10-16930264-G-C

Variant summary

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

The NM_001081.4(CUBN):​c.6125-1961C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,222 control chromosomes in the GnomAD database, including 53,210 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 0.83 (53210 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.6125-1961C>G		intron_variant		ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.6125-1961C>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126956 AN: 152104 Hom.: 53171 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.835 AC: 127052 AN: 152222 Hom.: 53210 Cov.: 33 AF XY: 0.835 AC XY: 62150 AN XY: 74418

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.851

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.845

Alfa AF: 0.807 Hom.: 6150

Bravo AF: 0.841

Asia WGS AF: 0.918 AC: 3192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.65

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: rs1276721; hg19: chr10-16972263;