rs3740165
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001081.4(CUBN):āc.7662A>Gā(p.Pro2554=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 1,614,024 control chromosomes in the GnomAD database, including 3,003 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.082 ( 864 hom., cov: 32)
Exomes š: 0.042 ( 2139 hom. )
Consequence
CUBN
NM_001081.4 synonymous
NM_001081.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.727
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=-0.59).
BP6
?
Variant 10-16907551-T-C is Benign according to our data. Variant chr10-16907551-T-C is described in ClinVar as [Benign]. Clinvar id is 299420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.727 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUBN | NM_001081.4 | c.7662A>G | p.Pro2554= | synonymous_variant | 49/67 | ENST00000377833.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUBN | ENST00000377833.10 | c.7662A>G | p.Pro2554= | synonymous_variant | 49/67 | 1 | NM_001081.4 | P1 | |
CUBN | ENST00000648092.1 | n.198A>G | non_coding_transcript_exon_variant | 1/4 | |||||
CUBN | ENST00000649933.1 | n.67+129A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0816 AC: 12417AN: 152118Hom.: 860 Cov.: 32
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GnomAD3 exomes AF: 0.0539 AC: 13551AN: 251476Hom.: 619 AF XY: 0.0506 AC XY: 6880AN XY: 135916
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GnomAD4 exome AF: 0.0421 AC: 61554AN: 1461788Hom.: 2139 Cov.: 33 AF XY: 0.0417 AC XY: 30288AN XY: 727202
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GnomAD4 genome ? AF: 0.0818 AC: 12450AN: 152236Hom.: 864 Cov.: 32 AF XY: 0.0809 AC XY: 6024AN XY: 74446
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Imerslund-Grasbeck syndrome type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2018 | - - |
Imerslund-Grasbeck syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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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