rs445160

Positions:

• chr4-2811776-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001122681.2(SH3BP2):​c.-4-8838C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 157,370 control chromosomes in the GnomAD database, including 33,110 homozygotes. 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 0.65 (32001 hom., cov: 33)
  • Exomes 𝑓: 0.62 (1109 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

Genes affected

SH3BP2 (HGNC:10825): (SH3 domain binding protein 2) The protein encoded by this gene has an N-terminal pleckstrin homology (PH) domain, an SH3-binding proline-rich region, and a C-terminal SH2 domain. The protein binds to the SH3 domains of several proteins including the ABL1 and SYK protein tyrosine kinases , and functions as a cytoplasmic adaptor protein to positively regulate transcriptional activity in T, natural killer (NK), and basophilic cells. Mutations in this gene result in cherubism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BP2	NM_001122681.2	c.-4-8838C>G		intron_variant		ENST00000503393.8	NP_001116153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8	c.-4-8838C>G		intron_variant		1	NM_001122681.2	ENSP00000422168	P2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98305 AN: 151954 Hom.: 31964 Cov.: 33

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.624 AC: 3307 AN: 5298 Hom.: 1109 Cov.: 0 AF XY: 0.627 AC XY: 1751 AN XY: 2792

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.751

Gnomad4 ASJ exome AF: 0.458

Gnomad4 EAS exome AF: 0.458

Gnomad4 SAS exome AF: 0.677

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.657

GnomAD4 genome AF: 0.647 AC: 98391 AN: 152072 Hom.: 32001 Cov.: 33 AF XY: 0.650 AC XY: 48331 AN XY: 74320

Gnomad4 AFR AF: 0.693

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.626

Alfa AF: 0.638 Hom.: 3870

Bravo AF: 0.654

Asia WGS AF: 0.661 AC: 2301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs445160; hg19: chr4-2813503;