4-2818442-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001122681.2(SH3BP2):c.-4-2172C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,006,900 control chromosomes in the GnomAD database, including 5,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (855 hom., cov: 33)
  • Exomes 𝑓: 0.098 (4260 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.83

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-2818442-C-G is Benign according to our data. Variant chr4-2818442-C-G is described in ClinVar as [Benign]. Clinvar id is 1226123.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.-4-2172C>G		intron_variant		ENST00000503393.8
SH3BP2	NM_001145855.2	c.81-2172C>G		intron_variant
SH3BP2	NM_001145856.2	c.167+52C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8	c.-4-2172C>G		intron_variant		1	NM_001122681.2	P2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15351 AN: 151474 Hom.: 855 Cov.: 33

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0984 AC: 84147 AN: 855320 Hom.: 4260 AF XY: 0.0990 AC XY: 40076 AN XY: 404970

Gnomad4 AFR exome AF: 0.0955

Gnomad4 AMR exome AF: 0.0567

Gnomad4 ASJ exome AF: 0.0924

Gnomad4 EAS exome AF: 0.00444

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.169

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.0904

GnomAD4 genome AF: 0.101 AC: 15352 AN: 151580 Hom.: 855 Cov.: 33 AF XY: 0.103 AC XY: 7662 AN XY: 74086

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.0705

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.0922

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0519 Hom.: 75

Bravo AF: 0.0915

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	-0.85
Cadd	Benign	2.3
Dann	Benign	0.21

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: rs28507721; hg19: chr4-2820169;