rs445160

Variant names:

• chr4-2811776-C-G
• rs445160
• NM_001122681.2:c.-4-8838C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

SH3BP2 Gene-Disease associations (from GenCC):

• cherubism

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122681.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	NM_001122681.2	MANE Select	c.-4-8838C>G		intron	N/A	NP_001116153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	ENST00000503393.8	TSL:1 MANE Select	c.-4-8838C>G		intron	N/A	ENSP00000422168.3
	SH3BP2	ENST00000503219.7	TSL:4	c.-5+1947C>G		intron	N/A	ENSP00000422796.2
	SH3BP2	ENST00000504294.6	TSL:5	c.-4-8838C>G		intron	N/A	ENSP00000423275.2

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

African (AFR) AF: 0.591 AC: 13 AN: 22

American (AMR) AF: 0.751 AC: 1038 AN: 1382

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 11 AN: 24

East Asian (EAS) AF: 0.458 AC: 99 AN: 216

South Asian (SAS) AF: 0.677 AC: 405 AN: 598

European-Finnish (FIN) AF: 0.607 AC: 34 AN: 56

Middle Eastern (MID) AF: 0.500 AC: 5 AN: 10

European-Non Finnish (NFE) AF: 0.562 AC: 1551 AN: 2760

Other (OTH) AF: 0.657 AC: 151 AN: 230

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

African (AFR) AF: 0.693 AC: 28759 AN: 41476

American (AMR) AF: 0.723 AC: 11052 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2204 AN: 3472

East Asian (EAS) AF: 0.539 AC: 2790 AN: 5172

South Asian (SAS) AF: 0.698 AC: 3368 AN: 4826

European-Finnish (FIN) AF: 0.624 AC: 6597 AN: 10564

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41503 AN: 67964

Other (OTH) AF: 0.626 AC: 1322 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.89
PhyloP100		-0.050
PromoterAI		0.047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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

Other links and lift over

dbSNP: rs445160; hg19: chr4-2813503;