rs4690002

chr4-2839513-T-Cchr4-2839513-T-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.*5679T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,978 control chromosomes in the GnomAD database, including 34,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.67 (34164 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH3BP2 NM_001122681.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.75

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=-1.06).
• BP6: Variant 4-2839513-T-C is Benign according to our data. Variant chr4-2839513-T-C is described in ClinVar as [Benign]. Clinvar id is 348689.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP2	NM_001122681.2	c.*5679T>C		3_prime_UTR_variant	13/13	ENST00000503393.8
SH3BP2	NM_001145855.2	c.*5679T>C		3_prime_UTR_variant	13/13
SH3BP2	NM_001145856.2	c.*5679T>C		3_prime_UTR_variant	13/13
SH3BP2	NM_003023.4	c.*5679T>C		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP2	ENST00000503393.8	c.*5679T>C		3_prime_UTR_variant	13/13	1	NM_001122681.2	P2
SH3BP2	ENST00000356331.9	c.*5679T>C		3_prime_UTR_variant	13/13	1		P2
SH3BP2	ENST00000435136.8	c.*5679T>C		3_prime_UTR_variant	13/13	2		A2

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101382 AN: 151862 Hom.: 34111 Cov.: 31

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.665

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 SAS exome AF: 0.00

GnomAD4 genome AF: 0.668 AC: 101491 AN: 151978 Hom.: 34164 Cov.: 31 AF XY: 0.668 AC XY: 49643 AN XY: 74274

Gnomad4 AFR AF: 0.745

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.669

Alfa AF: 0.625 Hom.: 3825

Bravo AF: 0.674

Asia WGS AF: 0.643 AC: 2236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fibrous dysplasia of jaw Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.57
Dann	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4690002; hg19: chr4-2841240;