NM_001387430.1:c.72T>A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_001387430.1(SH2B1):c.72T>A(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P24P) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000022 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SH2B1
NM_001387430.1 synonymous
NM_001387430.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.09
Publications
0 publications found
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]
SH2B1 Gene-Disease associations (from GenCC):
- severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiencyInheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -6 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 16-28866166-T-A is Benign according to our data. Variant chr16-28866166-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3351989.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-6.09 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001387430.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SH2B1 | NM_001387430.1 | MANE Select | c.72T>A | p.Pro24Pro | synonymous | Exon 1 of 8 | NP_001374359.1 | Q9NRF2-1 | |
| SH2B1 | NM_001145795.2 | c.72T>A | p.Pro24Pro | synonymous | Exon 2 of 9 | NP_001139267.1 | Q9NRF2-1 | ||
| SH2B1 | NM_001308293.2 | c.72T>A | p.Pro24Pro | synonymous | Exon 4 of 11 | NP_001295222.1 | Q9NRF2-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SH2B1 | ENST00000684370.1 | MANE Select | c.72T>A | p.Pro24Pro | synonymous | Exon 1 of 8 | ENSP00000507475.1 | Q9NRF2-1 | |
| SH2B1 | ENST00000618521.4 | TSL:1 | c.72T>A | p.Pro24Pro | synonymous | Exon 2 of 9 | ENSP00000481709.1 | Q9NRF2-1 | |
| SH2B1 | ENST00000359285.10 | TSL:1 | c.72T>A | p.Pro24Pro | synonymous | Exon 2 of 10 | ENSP00000352232.5 | Q9NRF2-3 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 124102Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
0
AN:
124102
Hom.:
Cov.:
31
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:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000216 AC: 23AN: 1063008Hom.: 0 Cov.: 37 AF XY: 0.0000249 AC XY: 13AN XY: 522738 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
23
AN:
1063008
Hom.:
Cov.:
37
AF XY:
AC XY:
13
AN XY:
522738
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
23450
American (AMR)
AF:
AC:
1
AN:
25294
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
15028
East Asian (EAS)
AF:
AC:
1
AN:
14018
South Asian (SAS)
AF:
AC:
0
AN:
69228
European-Finnish (FIN)
AF:
AC:
0
AN:
24850
Middle Eastern (MID)
AF:
AC:
0
AN:
3046
European-Non Finnish (NFE)
AF:
AC:
17
AN:
849194
Other (OTH)
AF:
AC:
2
AN:
38900
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.242
Heterozygous variant carriers
0
4
7
11
14
18
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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10
<30
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Age
GnomAD4 genome 0.00 AC: 0AN: 124140Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 60568
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
124140
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
60568
African (AFR)
AF:
AC:
0
AN:
33490
American (AMR)
AF:
AC:
0
AN:
12864
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3086
East Asian (EAS)
AF:
AC:
0
AN:
3694
South Asian (SAS)
AF:
AC:
0
AN:
3430
European-Finnish (FIN)
AF:
AC:
0
AN:
7150
Middle Eastern (MID)
AF:
AC:
0
AN:
260
European-Non Finnish (NFE)
AF:
AC:
0
AN:
57662
Other (OTH)
AF:
AC:
0
AN:
1772
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
-
-
1
SH2B1-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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