chr10-16955892-G-A

Variant names:

• chr10-16955892-G-A
• rs10508517
• NM_001081.4:c.4696-1344C>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.4696-1344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 152,140 control chromosomes in the GnomAD database, including 1,154 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 0.085 (1154 hom., cov: 33)
• Consequence: CUBN NM_001081.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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

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 = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUBN	NM_001081.4	c.4696-1344C>T		intron_variant	Intron 31 of 66	ENST00000377833.10	NP_001072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUBN	ENST00000377833.10	c.4696-1344C>T		intron_variant	Intron 31 of 66	1	NM_001081.4	ENSP00000367064.4

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12917 AN: 152022 Hom.: 1150 Cov.: 33

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0893

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0403

Gnomad OTH AF: 0.0824

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

GnomAD4 genome AF: 0.0850 AC: 12936 AN: 152140 Hom.: 1154 Cov.: 33 AF XY: 0.0930 AC XY: 6919 AN XY: 74372

African (AFR) AF: 0.0603 AC: 2503 AN: 41502

American (AMR) AF: 0.213 AC: 3250 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5168

South Asian (SAS) AF: 0.196 AC: 941 AN: 4812

European-Finnish (FIN) AF: 0.0893 AC: 945 AN: 10586

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0403 AC: 2738 AN: 68018

Other (OTH) AF: 0.0806 AC: 170 AN: 2110

Alfa AF: 0.0649 Hom.: 2472

Bravo AF: 0.0968

Asia WGS AF: 0.250 AC: 867 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	0.21
DANN	Benign	0.53
PhyloP100		-0.65
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

Publications

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Other links and lift over

dbSNP: rs10508517; hg19: chr10-16997891;