10-80609463-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001388272.1(SH2D4B):​c.900T>A​(p.Asp300Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,990 control chromosomes in the GnomAD database, including 23,937 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1990 hom., cov: 31)
Exomes 𝑓: 0.17 ( 21947 hom. )

Consequence

SH2D4B
NM_001388272.1 missense

Scores

1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

15 publications found
Variant links:
Genes affected
SH2D4B (HGNC:31440): (SH2 domain containing 4B) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003282398).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH2D4BNM_001388272.1 linkc.900T>A p.Asp300Glu missense_variant Exon 6 of 8 ENST00000646907.2 NP_001375201.1
SH2D4BNM_207372.2 linkc.897T>A p.Asp299Glu missense_variant Exon 6 of 7 NP_997255.2 Q5SQS7-2
SH2D4BNM_001145719.1 linkc.753T>A p.Asp251Glu missense_variant Exon 6 of 7 NP_001139191.1 Q5SQS7-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH2D4BENST00000646907.2 linkc.900T>A p.Asp300Glu missense_variant Exon 6 of 8 NM_001388272.1 ENSP00000494732.1 A0A2R8Y5Q0
SH2D4BENST00000339284.6 linkc.897T>A p.Asp299Glu missense_variant Exon 6 of 7 2 ENSP00000345295.2 Q5SQS7-2
SH2D4BENST00000313455.5 linkc.753T>A p.Asp251Glu missense_variant Exon 6 of 7 2 ENSP00000314242.4 Q5SQS7-3
SH2D4BENST00000372150.7 linkn.242T>A non_coding_transcript_exon_variant Exon 2 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.142
AC:
21554
AN:
152056
Hom.:
1992
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0476
Gnomad AMI
AF:
0.212
Gnomad AMR
AF:
0.146
Gnomad ASJ
AF:
0.180
Gnomad EAS
AF:
0.385
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.205
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.169
Gnomad OTH
AF:
0.145
GnomAD2 exomes
AF:
0.172
AC:
43286
AN:
251404
AF XY:
0.171
show subpopulations
Gnomad AFR exome
AF:
0.0444
Gnomad AMR exome
AF:
0.162
Gnomad ASJ exome
AF:
0.175
Gnomad EAS exome
AF:
0.369
Gnomad FIN exome
AF:
0.200
Gnomad NFE exome
AF:
0.170
Gnomad OTH exome
AF:
0.176
GnomAD4 exome
AF:
0.167
AC:
243889
AN:
1461816
Hom.:
21947
Cov.:
33
AF XY:
0.166
AC XY:
120431
AN XY:
727200
show subpopulations
African (AFR)
AF:
0.0445
AC:
1491
AN:
33480
American (AMR)
AF:
0.158
AC:
7054
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.177
AC:
4613
AN:
26134
East Asian (EAS)
AF:
0.398
AC:
15802
AN:
39700
South Asian (SAS)
AF:
0.117
AC:
10069
AN:
86254
European-Finnish (FIN)
AF:
0.192
AC:
10239
AN:
53418
Middle Eastern (MID)
AF:
0.164
AC:
948
AN:
5766
European-Non Finnish (NFE)
AF:
0.165
AC:
183562
AN:
1111956
Other (OTH)
AF:
0.167
AC:
10111
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.485
Heterozygous variant carriers
0
11340
22680
34019
45359
56699
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
6528
13056
19584
26112
32640
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.142
AC:
21543
AN:
152174
Hom.:
1990
Cov.:
31
AF XY:
0.145
AC XY:
10798
AN XY:
74378
show subpopulations
African (AFR)
AF:
0.0476
AC:
1978
AN:
41540
American (AMR)
AF:
0.146
AC:
2227
AN:
15298
Ashkenazi Jewish (ASJ)
AF:
0.180
AC:
625
AN:
3472
East Asian (EAS)
AF:
0.384
AC:
1979
AN:
5156
South Asian (SAS)
AF:
0.116
AC:
561
AN:
4822
European-Finnish (FIN)
AF:
0.205
AC:
2171
AN:
10582
Middle Eastern (MID)
AF:
0.150
AC:
44
AN:
294
European-Non Finnish (NFE)
AF:
0.169
AC:
11460
AN:
67986
Other (OTH)
AF:
0.144
AC:
305
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
921
1842
2762
3683
4604
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
238
476
714
952
1190
<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:
0.172
Hom.:
1754
Bravo
AF:
0.136
TwinsUK
AF:
0.171
AC:
634
ALSPAC
AF:
0.153
AC:
589
ESP6500AA
AF:
0.0533
AC:
235
ESP6500EA
AF:
0.170
AC:
1463
ExAC
AF:
0.169
AC:
20519
Asia WGS
AF:
0.222
AC:
771
AN:
3478
EpiCase
AF:
0.170
EpiControl
AF:
0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.87
T
BayesDel_noAF
Benign
-0.88
CADD
Benign
1.7
DANN
Benign
0.74
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0027
N
LIST_S2
Benign
0.66
T;T;T
MetaRNN
Benign
0.0033
T;T;T
MetaSVM
Benign
-1.0
T
PhyloP100
-1.0
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
1.5
N;.;N
REVEL
Benign
0.014
Sift
Benign
1.0
T;.;T
Sift4G
Benign
1.0
T;.;T
Polyphen
0.0010
B;.;B
Vest4
0.023
MPC
0.14
ClinPred
0.00077
T
GERP RS
-6.9
gMVP
0.11
Mutation Taster
=99/1
polymorphism (auto)

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: rs17107368; hg19: chr10-82369219; COSMIC: COSV57892844; API