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GeneBe

10-16863501-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001081.4(CUBN):c.9454+6135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,082 control chromosomes in the GnomAD database, including 4,415 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 0.22 ( 4415 hom., cov: 32)

Consequence

CUBN
NM_001081.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.334
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CUBNNM_001081.4 linkuse as main transcriptc.9454+6135G>A intron_variant ENST00000377833.10
CUBNXM_011519709.3 linkuse as main transcriptc.5440+6135G>A intron_variant
CUBNXM_011519710.3 linkuse as main transcriptc.5416+6135G>A intron_variant
CUBNXM_011519711.4 linkuse as main transcriptc.5296+6135G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CUBNENST00000377833.10 linkuse as main transcriptc.9454+6135G>A intron_variant 1 NM_001081.4 P1
CUBNENST00000649135.1 linkuse as main transcriptn.49+3306G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.220
AC:
33503
AN:
151964
Hom.:
4405
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.176
Gnomad AMI
AF:
0.293
Gnomad AMR
AF:
0.357
Gnomad ASJ
AF:
0.218
Gnomad EAS
AF:
0.609
Gnomad SAS
AF:
0.346
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.193
Gnomad NFE
AF:
0.179
Gnomad OTH
AF:
0.248
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.221
AC:
33538
AN:
152082
Hom.:
4415
Cov.:
32
AF XY:
0.230
AC XY:
17114
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.176
Gnomad4 AMR
AF:
0.357
Gnomad4 ASJ
AF:
0.218
Gnomad4 EAS
AF:
0.609
Gnomad4 SAS
AF:
0.346
Gnomad4 FIN
AF:
0.205
Gnomad4 NFE
AF:
0.179
Gnomad4 OTH
AF:
0.254
Alfa
AF:
0.195
Hom.:
3322
Bravo
AF:
0.235
Asia WGS
AF:
0.432
AC:
1502
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.93
Dann
Benign
0.64

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7893395; hg19: chr10-16905500; API