rs7898076

Positions:

• chr10-16834614-C-T

Variant summary

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

The NM_001081.4(CUBN):​c.10362+400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0686 in 152,238 control chromosomes in the GnomAD database, including 449 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 0.069 (449 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.10362+400G>A		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.6348+400G>A		intron_variant			XP_011518011.1
CUBN	XM_011519710.3	c.6324+400G>A		intron_variant			XP_011518012.1
CUBN	XM_011519711.4	c.6204+400G>A		intron_variant			XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.10362+400G>A		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.0686 AC: 10432 AN: 152120 Hom.: 443 Cov.: 32

Gnomad AFR AF: 0.0388

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0777

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0686 AC: 10447 AN: 152238 Hom.: 449 Cov.: 32 AF XY: 0.0709 AC XY: 5277 AN XY: 74416

Gnomad4 AFR AF: 0.0388

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0777

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0739 Hom.: 93

Bravo AF: 0.0595

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.60

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: rs7898076; hg19: chr10-16876613;