chr11-59831799-A-G
Position:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_005142.3(CBLIF):c.1074-3T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000636 in 1,431,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000062 ( 0 hom. )
Consequence
CBLIF
NM_005142.3 splice_region, splice_polypyrimidine_tract, intron
NM_005142.3 splice_region, splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00005151
2
Clinical Significance
Conservation
PhyloP100: 1.20
Genes affected
CBLIF (HGNC:4268): (cobalamin binding intrinsic factor) This gene is a member of the cobalamin transport protein family. It encodes a glycoprotein secreted by parietal cells of the gastric mucosa and is required for adequate absorption of vitamin B12. Vitamin B12 is necessary for erythrocyte maturation and mutations in this gene may lead to congenital pernicious anemia. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 11-59831799-A-G is Benign according to our data. Variant chr11-59831799-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 800190.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000618 (79/1279340) while in subpopulation AMR AF= 0.00164 (73/44406). AF 95% confidence interval is 0.00134. There are 0 homozygotes in gnomad4_exome. There are 24 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| CBLIF | NM_005142.3 | c.1074-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000257248.3 | |||
| CBLIF | XM_011544939.4 | c.1032-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CBLIF | ENST00000257248.3 | c.1074-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_005142.3 | P1 | |||
| CBLIF | ENST00000525058.5 | c.*1041-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 2 | |||||
| CBLIF | ENST00000533067.1 | n.121-3T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes 0.0000790 AC: 12AN: 151956Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
12
AN:
151956
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000307 AC: 77AN: 251004Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135664
GnomAD3 exomes
AF:
AC:
77
AN:
251004
Hom.:
AF XY:
AC XY:
22
AN XY:
135664
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000618 AC: 79AN: 1279340Hom.: 0 Cov.: 21 AF XY: 0.0000372 AC XY: 24AN XY: 645698
GnomAD4 exome
AF:
AC:
79
AN:
1279340
Hom.:
Cov.:
21
AF XY:
AC XY:
24
AN XY:
645698
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.0000790 AC: 12AN: 151956Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74246
GnomAD4 genome
AF:
AC:
12
AN:
151956
Hom.:
Cov.:
32
AF XY:
AC XY:
6
AN XY:
74246
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary intrinsic factor deficiency Uncertain:1Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 16, 2020 | - - |
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
CBLIF-related disorder Benign:1
| Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 08, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at