chrX-81250486-G-A

Variant summary

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

The NM_003022.3(SH3BGRL):​c.46-26498G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 110,278 control chromosomes in the GnomAD database, including 2,195 homozygotes. There are 7,272 hemizygotes in GnomAD. 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 0.22 ( 2195 hom., 7272 hem., cov: 22)

Consequence

SH3BGRL
NM_003022.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

1 publications found
Variant links:
Genes affected
SH3BGRL (HGNC:10823): (SH3 domain binding glutamate rich protein like) Predicted to enable SH3 domain binding activity. Located in extracellular exosome. [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 (BayesDel_noAF=-0.98).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SH3BGRLNM_003022.3 linkc.46-26498G>A intron_variant Intron 1 of 3 ENST00000373212.6 NP_003013.1 O75368V9HW48
SH3BGRLXM_011531013.1 linkc.231+13206G>A intron_variant Intron 2 of 4 XP_011529315.1
SH3BGRLXM_011531014.2 linkc.156+13206G>A intron_variant Intron 3 of 5 XP_011529316.1
SH3BGRLXM_047442354.1 linkc.156+13206G>A intron_variant Intron 2 of 4 XP_047298310.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SH3BGRLENST00000373212.6 linkc.46-26498G>A intron_variant Intron 1 of 3 1 NM_003022.3 ENSP00000362308.5 O75368
SH3BGRLENST00000481106.5 linkn.259-26498G>A intron_variant Intron 2 of 4 1
SH3BGRLENST00000463546.5 linkn.92-26498G>A intron_variant Intron 1 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.222
AC:
24508
AN:
110249
Hom.:
2196
Cov.:
22
show subpopulations
Gnomad AFR
AF:
0.215
Gnomad AMI
AF:
0.0815
Gnomad AMR
AF:
0.190
Gnomad ASJ
AF:
0.182
Gnomad EAS
AF:
0.695
Gnomad SAS
AF:
0.412
Gnomad FIN
AF:
0.218
Gnomad MID
AF:
0.239
Gnomad NFE
AF:
0.197
Gnomad OTH
AF:
0.218
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.222
AC:
24524
AN:
110278
Hom.:
2195
Cov.:
22
AF XY:
0.223
AC XY:
7272
AN XY:
32638
show subpopulations
African (AFR)
AF:
0.215
AC:
6547
AN:
30427
American (AMR)
AF:
0.190
AC:
1995
AN:
10500
Ashkenazi Jewish (ASJ)
AF:
0.182
AC:
479
AN:
2637
East Asian (EAS)
AF:
0.695
AC:
2415
AN:
3477
South Asian (SAS)
AF:
0.416
AC:
1075
AN:
2584
European-Finnish (FIN)
AF:
0.218
AC:
1210
AN:
5563
Middle Eastern (MID)
AF:
0.236
AC:
50
AN:
212
European-Non Finnish (NFE)
AF:
0.197
AC:
10369
AN:
52702
Other (OTH)
AF:
0.219
AC:
329
AN:
1501
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
677
1354
2032
2709
3386
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
274
548
822
1096
1370
<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:
0.218
Hom.:
4658
Bravo
AF:
0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
1.0
DANN
Benign
0.51
PhyloP100
0.20
Mutation Taster
=100/0
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: rs12389790; hg19: chrX-80505985; API