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GeneBe

rs7498665

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387430.1(SH2B1):c.1450A>G(p.Thr484Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 146026 control chromosomes in the gnomAD Genomes database, including 9247 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.35 ( 9247 hom., cov: 23)
Exomes 𝑓: 0.35 ( 17007 hom. )

Consequence

SH2B1
NM_001387430.1 missense

Scores

1
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.432

Links

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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 (MetaRNN=6.3735247E-4).
BP6
?
Variant 16-28871920-A-G is Benign according to our data. Variant chr16-28871920-A-G is described in ClinVar as [Benign]. Clinvar id is 1232867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SH2B1NM_001387430.1 linkuse as main transcriptc.1450A>G p.Thr484Ala missense_variant 5/8 ENST00000684370.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SH2B1ENST00000684370.1 linkuse as main transcriptc.1450A>G p.Thr484Ala missense_variant 5/8 NM_001387430.1 P3Q9NRF2-1

Frequencies

GnomAD3 genomes
AF:
0.346
AC:
50546
AN:
146026
Hom.:
9247
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.270
Gnomad AMI
AF:
0.242
Gnomad AMR
AF:
0.408
Gnomad ASJ
AF:
0.270
Gnomad EAS
AF:
0.124
Gnomad SAS
AF:
0.227
Gnomad FIN
AF:
0.433
Gnomad MID
AF:
0.234
Gnomad NFE
AF:
0.395
Gnomad OTH
AF:
0.309
GnomAD3 exomes
AF:
0.351
AC:
87551
AN:
249400
Hom.:
17007
AF XY:
0.343
AC XY:
46316
AN XY:
134960
show subpopulations
Gnomad AFR exome
AF:
0.270
Gnomad AMR exome
AF:
0.488
Gnomad ASJ exome
AF:
0.275
Gnomad EAS exome
AF:
0.102
Gnomad SAS exome
AF:
0.229
Gnomad FIN exome
AF:
0.425
Gnomad NFE exome
AF:
0.388
Gnomad OTH exome
AF:
0.347
GnomAD4 exome
AF:
0.379
AC:
538478
AN:
1419620
Hom.:
105062
AF XY:
0.375
AC XY:
265080
AN XY:
707606
show subpopulations
Gnomad4 AFR exome
AF:
0.261
Gnomad4 AMR exome
AF:
0.493
Gnomad4 ASJ exome
AF:
0.278
Gnomad4 EAS exome
AF:
0.141
Gnomad4 SAS exome
AF:
0.228
Gnomad4 FIN exome
AF:
0.436
Gnomad4 NFE exome
AF:
0.400
Gnomad4 OTH exome
AF:
0.352
Alfa
AF:
0.370
Hom.:
5748
Bravo
AF:
0.339
TwinsUK
AF:
0.396
AC:
1468
ALSPAC
AF:
0.401
AC:
1545
ESP6500AA
AF:
0.270
AC:
1188
ESP6500EA
AF:
0.381
AC:
3280
ExAC
AF:
0.345
AC:
41888
Asia WGS
AF:
0.275
AC:
953
AN:
3478
EpiCase
AF:
0.358
EpiControl
AF:
0.354

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 19, 2021This variant is associated with the following publications: (PMID: 19079261, 21912638, 23818875, 24971614, 23270367) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.047
BayesDel_addAF
Benign
-0.79
T
BayesDel_noAF
Benign
-0.76
Cadd
Benign
13
Dann
Benign
0.34
DEOGEN2
Benign
0.056
T;.;T;T;.;T;.;.
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.0092
N
MetaRNN
Benign
0.00064
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N;N;.;N;N;.;N;.
MutationTaster
Benign
1.0
P;P;P;P
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.050
N;N;N;.;N;N;N;N
REVEL
Benign
0.030
Sift
Benign
1.0
T;T;T;.;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T;T;T;T
Polyphen
0.0
B;B;B;B;B;B;B;.
Vest4
0.015
MPC
0.23
ClinPred
0.0021
T
GERP RS
3.1
Varity_R
0.018
gMVP
0.13

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs7498665; hg19: chr16-28883241; COSMIC: COSV59461486; COSMIC: COSV59461486; API