rs12254816

Positions:

• chr10-17072789-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.2302-818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,108 control chromosomes in the GnomAD database, including 988 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 0.11 (988 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.2302-818A>G		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519708.3	c.2302-818A>G		intron_variant			XP_011518010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.2302-818A>G		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16957 AN: 151990 Hom.: 986 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0758

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0953

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

GnomAD4 genome AF: 0.112 AC: 16974 AN: 152108 Hom.: 988 Cov.: 32 AF XY: 0.109 AC XY: 8136 AN XY: 74350

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.108 Hom.: 1096

Bravo AF: 0.107

Asia WGS AF: 0.0980 AC: 338 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.7
DANN	Benign	0.78

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: rs12254816; hg19: chr10-17114788;