4-2820562-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122681.2(SH3BP2):c.-4-52C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,611,824 control chromosomes in the GnomAD database, including 243,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (22984 hom., cov: 34)
  • Exomes 𝑓: 0.55 (220406 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.32

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-2820562-C-A is Benign according to our data. Variant chr4-2820562-C-A is described in ClinVar as [Benign]. Clinvar id is 1256910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP2	NM_001122681.2	c.-4-52C>A		intron_variant		ENST00000503393.8
SH3BP2	NM_001145855.2	c.81-52C>A		intron_variant
SH3BP2	NM_001145856.2	c.168-52C>A		intron_variant
SH3BP2	NM_003023.4	c.-4-52C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8	c.-4-52C>A		intron_variant		1	NM_001122681.2	P2

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83259 AN: 152048 Hom.: 22959 Cov.: 34

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.548 AC: 799673 AN: 1459656 Hom.: 220406 AF XY: 0.549 AC XY: 398552 AN XY: 726166

Gnomad4 AFR exome AF: 0.534

Gnomad4 AMR exome AF: 0.672

Gnomad4 ASJ exome AF: 0.539

Gnomad4 EAS exome AF: 0.465

Gnomad4 SAS exome AF: 0.597

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.550

GnomAD4 genome AF: 0.548 AC: 83325 AN: 152168 Hom.: 22984 Cov.: 34 AF XY: 0.547 AC XY: 40694 AN XY: 74386

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.549

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.546

Alfa AF: 0.535 Hom.: 2727

Bravo AF: 0.559

Asia WGS AF: 0.551 AC: 1914 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 88% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.7
Dann	Benign	0.75

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: rs2239727; hg19: chr4-2822289; COSMIC: COSV62553770; COSMIC: COSV62553770;