rs7897705

Positions:

• chr10-16834375-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+639G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,086 control chromosomes in the GnomAD database, including 938 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 (938 hom., cov: 32)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUBN	NM_001081.4	c.10362+639G>A		intron_variant		ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.6348+639G>A		intron_variant			XP_011518011.1
CUBN	XM_011519710.3	c.6324+639G>A		intron_variant			XP_011518012.1
CUBN	XM_011519711.4	c.6204+639G>A		intron_variant			XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.10362+639G>A		intron_variant		1	NM_001081.4	ENSP00000367064	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15643 AN: 151968 Hom.: 931 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0514

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.103 AC: 15666 AN: 152086 Hom.: 938 Cov.: 32 AF XY: 0.105 AC XY: 7826 AN XY: 74348

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0514

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0904

Alfa AF: 0.0937 Hom.: 100

Bravo AF: 0.0965

Asia WGS AF: 0.151 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.75

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: rs7897705; hg19: chr10-16876374;