rs7897716

chr10-16834452-A-Cchr10-16834452-A-Gchr10-16834452-A-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+562T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,036 control chromosomes in the GnomAD database, including 2,847 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 0.18 (2847 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.10362+562T>G		intron_variant		ENST00000377833.10
CUBN	XM_011519709.3	c.6348+562T>G		intron_variant
CUBN	XM_011519710.3	c.6324+562T>G		intron_variant
CUBN	XM_011519711.4	c.6204+562T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.10362+562T>G		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26604 AN: 151918 Hom.: 2831 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.175 AC: 26657 AN: 152036 Hom.: 2847 Cov.: 32 AF XY: 0.182 AC XY: 13488 AN XY: 74304

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.162

Alfa AF: 0.122 Hom.: 477

Bravo AF: 0.173

Asia WGS AF: 0.345 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.52

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: rs7897716; hg19: chr10-16876451;