rs79801018

Positions:

• chr10-16895660-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.8598+3336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,204 control chromosomes in the GnomAD database, including 839 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 0.10 (839 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.8598+3336A>G		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.4584+3336A>G		intron_variant
CUBN	XM_011519710.3	c.4560+3336A>G		intron_variant
CUBN	XM_011519711.4	c.4440+3336A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.8598+3336A>G		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15752 AN: 152086 Hom.: 835 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0783

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.104 AC: 15778 AN: 152204 Hom.: 839 Cov.: 32 AF XY: 0.101 AC XY: 7521 AN XY: 74436

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0783

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.114

Alfa AF: 0.109 Hom.: 126

Bravo AF: 0.105

Asia WGS AF: 0.0630 AC: 220 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.42
DANN	Benign	0.72

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: rs79801018; hg19: chr10-16937659;