rs3213501

Variant names:

• chr4-2824673-T-C
• rs3213501
• NM_001122681.2:c.300T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001122681.2(SH3BP2):​c.300T>C​(p.His100His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,482 control chromosomes in the GnomAD database, including 442,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.80 (49106 hom., cov: 32)
  • Exomes 𝑓: 0.73 (393109 hom.)
• Consequence: SH3BP2 NM_001122681.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8 O:1
• Conservation: PhyloP100: 2.40
• Publications: 27 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), Orphanet, G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 4-2824673-T-C is Benign according to our data. Variant chr4-2824673-T-C is described in ClinVar as Benign. ClinVar VariationId is 258894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.4 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	NM_001122681.2	MANE Select	c.300T>C	p.His100His	synonymous	Exon 4 of 13	NP_001116153.1	A0A384N6E5
	SH3BP2	NM_001145856.2		c.471T>C	p.His157His	synonymous	Exon 4 of 13	NP_001139328.1	P78314-4
	SH3BP2	NM_001145855.2		c.384T>C	p.His128His	synonymous	Exon 4 of 13	NP_001139327.1	P78314-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	ENST00000503393.8	TSL:1 MANE Select	c.300T>C	p.His100His	synonymous	Exon 4 of 13	ENSP00000422168.3	P78314-1
	SH3BP2	ENST00000511747.6	TSL:1	c.471T>C	p.His157His	synonymous	Exon 4 of 13	ENSP00000424846.2	P78314-4
	SH3BP2	ENST00000356331.10	TSL:1	n.561T>C		non_coding_transcript_exon	Exon 4 of 13

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120842 AN: 151986 Hom.: 49039 Cov.: 32

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.783

GnomAD2 exomes AF: 0.755 AC: 189528 AN: 251054 AF XY: 0.752

Gnomad AFR exome AF: 0.956

Gnomad AMR exome AF: 0.887

Gnomad ASJ exome AF: 0.729

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.724

Gnomad OTH exome AF: 0.762

GnomAD4 exome AF: 0.731 AC: 1067538 AN: 1461378 Hom.: 393109 Cov.: 52 AF XY: 0.732 AC XY: 532408 AN XY: 727004

African (AFR) AF: 0.961 AC: 32184 AN: 33478

American (AMR) AF: 0.882 AC: 39424 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 19105 AN: 26136

East Asian (EAS) AF: 0.532 AC: 21105 AN: 39696

South Asian (SAS) AF: 0.811 AC: 69961 AN: 86252

European-Finnish (FIN) AF: 0.683 AC: 36377 AN: 53272

Middle Eastern (MID) AF: 0.854 AC: 4925 AN: 5768

European-Non Finnish (NFE) AF: 0.719 AC: 799512 AN: 1111682

Other (OTH) AF: 0.744 AC: 44945 AN: 60380

GnomAD4 genome AF: 0.795 AC: 120967 AN: 152104 Hom.: 49106 Cov.: 32 AF XY: 0.794 AC XY: 59003 AN XY: 74332

African (AFR) AF: 0.951 AC: 39520 AN: 41544

American (AMR) AF: 0.855 AC: 13079 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2580 AN: 3472

East Asian (EAS) AF: 0.542 AC: 2784 AN: 5134

South Asian (SAS) AF: 0.798 AC: 3853 AN: 4826

European-Finnish (FIN) AF: 0.682 AC: 7210 AN: 10572

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.725 AC: 49283 AN: 67950

Other (OTH) AF: 0.785 AC: 1655 AN: 2108

Alfa AF: 0.759 Hom.: 111873

Bravo AF: 0.813

Asia WGS AF: 0.732 AC: 2546 AN: 3478

EpiCase AF: 0.741

EpiControl AF: 0.739

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fibrous dysplasia of jaw (3)
-	-	3	not specified (3)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.63
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs3213501; hg19: chr4-2826400; COSMIC: COSV62554145; COSMIC: COSV62554145;