rs150309054
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001081.4(CUBN):c.963C>T(p.Pro321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,614,194 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0057 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00080 ( 12 hom. )
Consequence
CUBN
NM_001081.4 synonymous
NM_001081.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.717
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-17110971-G-A is Benign according to our data. Variant chr10-17110971-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 299532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.717 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00568 (865/152326) while in subpopulation AFR AF= 0.0185 (769/41564). AF 95% confidence interval is 0.0174. There are 3 homozygotes in gnomad4. There are 407 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUBN | NM_001081.4 | c.963C>T | p.Pro321= | synonymous_variant | 9/67 | ENST00000377833.10 | |
CUBN | XM_011519708.3 | c.963C>T | p.Pro321= | synonymous_variant | 9/55 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUBN | ENST00000377833.10 | c.963C>T | p.Pro321= | synonymous_variant | 9/67 | 1 | NM_001081.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00569 AC: 866AN: 152208Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00171 AC: 430AN: 251394Hom.: 6 AF XY: 0.00122 AC XY: 166AN XY: 135870
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GnomAD4 exome AF: 0.000798 AC: 1166AN: 1461868Hom.: 12 Cov.: 33 AF XY: 0.000704 AC XY: 512AN XY: 727238
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GnomAD4 genome ? AF: 0.00568 AC: 865AN: 152326Hom.: 3 Cov.: 33 AF XY: 0.00547 AC XY: 407AN XY: 74468
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 10, 2023 | - - |
Imerslund-Grasbeck syndrome type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Imerslund-Grasbeck syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at