rs7906195

Positions:

• chr10-17103666-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.1418-429A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0745 in 152,282 control chromosomes in the GnomAD database, including 886 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 0.075 (886 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUBN	NM_001081.4	c.1418-429A>G		intron_variant		ENST00000377833.10
CUBN	XM_011519708.3	c.1418-429A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUBN	ENST00000377833.10	c.1418-429A>G		intron_variant		1	NM_001081.4	P1

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11335 AN: 152162 Hom.: 883 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0361

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.0631

Gnomad SAS AF: 0.0254

Gnomad FIN AF: 0.0260

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0237

Gnomad OTH AF: 0.0545

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

GnomAD4 genome AF: 0.0745 AC: 11351 AN: 152282 Hom.: 886 Cov.: 32 AF XY: 0.0723 AC XY: 5381 AN XY: 74472

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.0629

Gnomad4 SAS AF: 0.0250

Gnomad4 FIN AF: 0.0260

Gnomad4 NFE AF: 0.0237

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0427 Hom.: 157

Bravo AF: 0.0813

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.49

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: rs7906195; hg19: chr10-17145665;