4-2818534-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001122681.2(SH3BP2):c.-4-2080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 521,254 control chromosomes in the GnomAD database, including 2,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (865 hom., cov: 33)
  • Exomes 𝑓: 0.085 (1579 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.510

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=-0.44).
• BP6: Variant 4-2818534-G-A is Benign according to our data. Variant chr4-2818534-G-A is described in ClinVar as [Benign]. Clinvar id is 1264442.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP2	NM_001122681.2	c.-4-2080G>A		intron_variant		ENST00000503393.8
SH3BP2	NM_001145855.2	c.81-2080G>A		intron_variant
SH3BP2	NM_001145856.2	c.167+144G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8	c.-4-2080G>A		intron_variant		1	NM_001122681.2	P2

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15466 AN: 152114 Hom.: 865 Cov.: 33

Gnomad AFR AF: 0.0917

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.0861

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0847 AC: 31248 AN: 369032 Hom.: 1579 AF XY: 0.0851 AC XY: 15160 AN XY: 178056

Gnomad4 AFR exome AF: 0.0775

Gnomad4 AMR exome AF: 0.0517

Gnomad4 ASJ exome AF: 0.0798

Gnomad4 EAS exome AF: 0.00436

Gnomad4 SAS exome AF: 0.0815

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.0860

Gnomad4 OTH exome AF: 0.0768

GnomAD4 genome AF: 0.102 AC: 15466 AN: 152222 Hom.: 865 Cov.: 33 AF XY: 0.104 AC XY: 7719 AN XY: 74416

Gnomad4 AFR AF: 0.0915

Gnomad4 AMR AF: 0.0710

Gnomad4 ASJ AF: 0.0861

Gnomad4 EAS AF: 0.0110

Gnomad4 SAS AF: 0.0902

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0660 Hom.: 88

Bravo AF: 0.0918

Asia WGS AF: 0.0540 AC: 189 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	17
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs28562583; hg19: chr4-2820261;