8-11550274-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001715.3(BLK):c.472+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,612,548 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0061 ( 11 hom., cov: 33)
Exomes 𝑓: 0.00091 ( 8 hom. )
Consequence
BLK
NM_001715.3 intron
NM_001715.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.39
Genes affected
BLK (HGNC:1057): (BLK proto-oncogene, Src family tyrosine kinase) This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 8-11550274-G-A is Benign according to our data. Variant chr8-11550274-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 258178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-11550274-G-A is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00611 (931/152342) while in subpopulation AFR AF= 0.0202 (841/41578). AF 95% confidence interval is 0.0191. There are 11 homozygotes in gnomad4. There are 438 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 931 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BLK | NM_001715.3 | c.472+12G>A | intron_variant | ENST00000259089.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BLK | ENST00000259089.9 | c.472+12G>A | intron_variant | 1 | NM_001715.3 | P1 | |||
BLK | ENST00000526778.1 | n.269+12G>A | intron_variant, non_coding_transcript_variant | 3 | |||||
BLK | ENST00000645242.1 | n.623+12G>A | intron_variant, non_coding_transcript_variant | ||||||
BLK | ENST00000696154.2 | n.623+12G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00606 AC: 923AN: 152224Hom.: 11 Cov.: 33
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GnomAD3 exomes AF: 0.00183 AC: 460AN: 250932Hom.: 2 AF XY: 0.00149 AC XY: 202AN XY: 135710
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GnomAD4 exome AF: 0.000914 AC: 1335AN: 1460206Hom.: 8 Cov.: 31 AF XY: 0.000830 AC XY: 603AN XY: 726430
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GnomAD4 genome AF: 0.00611 AC: 931AN: 152342Hom.: 11 Cov.: 33 AF XY: 0.00588 AC XY: 438AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Maturity-onset diabetes of the young type 11 Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 07, 2023 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Systemic lupus erythematosus Benign:1
Benign, criteria provided, single submitter | research | Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic | - | BLK gene is associated with Systemic lupus erythematosus, sjogren's syndrome and other systemic inflammatory conditions. However no sufficient evidence is found to ascertain the role of this particular variant rs145058498, yet. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at