chr16-28866205-G-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001387430.1(SH2B1):c.111G>T(p.Ala37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000562 in 1,601,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SH2B1
NM_001387430.1 synonymous
NM_001387430.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.02
Genes affected
SH2B1 (HGNC:30417): (SH2B adaptor protein 1) This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 16-28866205-G-T is Benign according to our data. Variant chr16-28866205-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2889595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.02 with no splicing effect.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SH2B1 | NM_001387430.1 | c.111G>T | p.Ala37= | synonymous_variant | 1/8 | ENST00000684370.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SH2B1 | ENST00000684370.1 | c.111G>T | p.Ala37= | synonymous_variant | 1/8 | NM_001387430.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151750Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000225 AC: 5AN: 222302Hom.: 0 AF XY: 0.0000163 AC XY: 2AN XY: 122880
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GnomAD4 exome AF: 0.00000207 AC: 3AN: 1449316Hom.: 0 Cov.: 35 AF XY: 0.00000139 AC XY: 1AN XY: 720450
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SH2B1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 15, 2022 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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