rs16843413

Variant names:

• chr4-2825185-C-G
• rs16843413
• NM_001122681.2:c.417C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-2825185-C-G
• chr4-2825185-C-T

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.417C>G​(p.Pro139Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,580,238 control chromosomes in the GnomAD database, including 6,933 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1815 hom., cov: 34)
  • Exomes 𝑓: 0.075 (5118 hom.)
• Consequence: SH3BP2 NM_001122681.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.51
• Publications: 6 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), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 4-2825185-C-G is Benign according to our data. Variant chr4-2825185-C-G is described in ClinVar as Benign. ClinVar VariationId is 258896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.51 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	NM_001122681.2	MANE Select	c.417C>G	p.Pro139Pro	synonymous	Exon 5 of 13	NP_001116153.1
	SH3BP2	NM_001145856.2		c.588C>G	p.Pro196Pro	synonymous	Exon 5 of 13	NP_001139328.1
	SH3BP2	NM_001145855.2		c.501C>G	p.Pro167Pro	synonymous	Exon 5 of 13	NP_001139327.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP2	ENST00000503393.8	TSL:1 MANE Select	c.417C>G	p.Pro139Pro	synonymous	Exon 5 of 13	ENSP00000422168.3
	SH3BP2	ENST00000511747.6	TSL:1	c.588C>G	p.Pro196Pro	synonymous	Exon 5 of 13	ENSP00000424846.2
	SH3BP2	ENST00000356331.10	TSL:1	n.678C>G		non_coding_transcript_exon	Exon 5 of 13

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18703 AN: 152056 Hom.: 1808 Cov.: 34

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0741

Gnomad EAS AF: 0.0557

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.108

GnomAD2 exomes AF: 0.0885 AC: 17180 AN: 194026 AF XY: 0.0857

Gnomad AFR exome AF: 0.260

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.0629

Gnomad EAS exome AF: 0.0599

Gnomad FIN exome AF: 0.0170

Gnomad NFE exome AF: 0.0628

Gnomad OTH exome AF: 0.0864

GnomAD4 exome AF: 0.0753 AC: 107489 AN: 1428062 Hom.: 5118 Cov.: 32 AF XY: 0.0753 AC XY: 53297 AN XY: 707406

African (AFR) AF: 0.273 AC: 8877 AN: 32534

American (AMR) AF: 0.136 AC: 5434 AN: 39874

Ashkenazi Jewish (ASJ) AF: 0.0633 AC: 1617 AN: 25540

East Asian (EAS) AF: 0.0550 AC: 2076 AN: 37726

South Asian (SAS) AF: 0.113 AC: 9223 AN: 81762

European-Finnish (FIN) AF: 0.0196 AC: 996 AN: 50926

Middle Eastern (MID) AF: 0.105 AC: 602 AN: 5718

European-Non Finnish (NFE) AF: 0.0673 AC: 73701 AN: 1094960

Other (OTH) AF: 0.0841 AC: 4963 AN: 59022

GnomAD4 genome AF: 0.123 AC: 18738 AN: 152176 Hom.: 1815 Cov.: 34 AF XY: 0.120 AC XY: 8964 AN XY: 74410

African (AFR) AF: 0.262 AC: 10888 AN: 41492

American (AMR) AF: 0.121 AC: 1848 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0741 AC: 257 AN: 3470

East Asian (EAS) AF: 0.0558 AC: 288 AN: 5160

South Asian (SAS) AF: 0.113 AC: 545 AN: 4826

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0650 AC: 4417 AN: 67988

Other (OTH) AF: 0.107 AC: 225 AN: 2112

Alfa AF: 0.0799 Hom.: 236

Bravo AF: 0.137

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.2
DANN	Benign	0.59
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs16843413; hg19: chr4-2826912; COSMIC: COSV62553681; COSMIC: COSV62553681;