rs7897705

Variant names:

• chr10-16834375-C-T
• rs7897705
• NM_001081.4:c.10362+639G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

CUBN Gene-Disease associations (from GenCC):

• Imerslund-Grasbeck syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• proteinuria, chronic benign

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Imerslund-Grasbeck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.10362+639G>A		intron_variant	Intron 64 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.6348+639G>A		intron_variant	Intron 38 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.6324+639G>A		intron_variant	Intron 38 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.6204+639G>A		intron_variant	Intron 37 of 39		XP_011518013.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.10362+639G>A		intron_variant	Intron 64 of 66	1	NM_001081.4	ENSP00000367064.4

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

African (AFR) AF: 0.144 AC: 5981 AN: 41494

American (AMR) AF: 0.0514 AC: 785 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0484 AC: 168 AN: 3468

East Asian (EAS) AF: 0.145 AC: 749 AN: 5150

South Asian (SAS) AF: 0.107 AC: 513 AN: 4814

European-Finnish (FIN) AF: 0.159 AC: 1679 AN: 10562

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0804 AC: 5468 AN: 67996

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0942 Hom.: 108

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
PhyloP100		-0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7897705; hg19: chr10-16876374;