chr16-28871086-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001387430.1(SH2B1):​c.1310-694C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000395 in 152,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 31)

Consequence

SH2B1
NM_001387430.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.315

Publications

1 publications found
Variant links:
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 deficiency
    Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS2
High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH2B1NM_001387430.1 linkc.1310-694C>T intron_variant Intron 4 of 7 ENST00000684370.1 NP_001374359.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH2B1ENST00000684370.1 linkc.1310-694C>T intron_variant Intron 4 of 7 NM_001387430.1 ENSP00000507475.1 Q9NRF2-1

Frequencies

GnomAD3 genomes
AF:
0.000395
AC:
60
AN:
151884
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000315
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000525
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00617
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000479
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.000395
AC:
60
AN:
152002
Hom.:
0
Cov.:
31
AF XY:
0.000390
AC XY:
29
AN XY:
74274
show subpopulations
African (AFR)
AF:
0.000314
AC:
13
AN:
41456
American (AMR)
AF:
0.000525
AC:
8
AN:
15252
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00618
AC:
32
AN:
5178
South Asian (SAS)
AF:
0.000208
AC:
1
AN:
4800
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10562
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000736
AC:
5
AN:
67976
Other (OTH)
AF:
0.000474
AC:
1
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
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

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000699
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
4.2
DANN
Benign
0.76
PhyloP100
-0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs12599217; hg19: chr16-28882407; API