rs7897716

Variant names:

• chr10-16834452-A-C
• rs7897716
• NM_001081.4:c.10362+562T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-16834452-A-C
• chr10-16834452-A-G
• chr10-16834452-A-T

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+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
• 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=-0.91).
• 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 rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.10362+562T>G		intron_variant	Intron 64 of 66	ENST00000377833.10	NP_001072.2
CUBN	XM_011519709.3	c.6348+562T>G		intron_variant	Intron 38 of 40		XP_011518011.1
CUBN	XM_011519710.3	c.6324+562T>G		intron_variant	Intron 38 of 40		XP_011518012.1
CUBN	XM_011519711.4	c.6204+562T>G		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+562T>G		intron_variant	Intron 64 of 66	1	NM_001081.4	ENSP00000367064.4

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

African (AFR) AF: 0.234 AC: 9719 AN: 41454

American (AMR) AF: 0.132 AC: 2018 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 383 AN: 3466

East Asian (EAS) AF: 0.460 AC: 2376 AN: 5162

South Asian (SAS) AF: 0.189 AC: 910 AN: 4816

European-Finnish (FIN) AF: 0.236 AC: 2492 AN: 10572

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8101 AN: 67962

Other (OTH) AF: 0.162 AC: 341 AN: 2108

Alfa AF: 0.125 Hom.: 591

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
PhyloP100		-0.37
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: rs7897716; hg19: chr10-16876451;