rs56323343

Variant names:

• chr4-2820580-T-C
• rs56323343
• NM_001122681.2:c.-4-34T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122681.2(SH3BP2):​c.-4-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,698 control chromosomes in the GnomAD database, including 8,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (893 hom., cov: 34)
  • Exomes 𝑓: 0.10 (7958 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.121
• Publications: 2 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 4-2820580-T-C is Benign according to our data. Variant chr4-2820580-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 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.-4-34T>C		intron	N/A	NP_001116153.1	A0A384N6E5
	SH3BP2	NM_001145856.2		c.168-34T>C		intron	N/A	NP_001139328.1	P78314-4
	SH3BP2	NM_001145855.2		c.81-34T>C		intron	N/A	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.-4-34T>C		intron	N/A	ENSP00000422168.3	P78314-1
	SH3BP2	ENST00000511747.6	TSL:1	c.168-34T>C		intron	N/A	ENSP00000424846.2	P78314-4
	SH3BP2	ENST00000356331.10	TSL:1	n.258-34T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15752 AN: 152170 Hom.: 893 Cov.: 34

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.0918

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0974 AC: 24466 AN: 251284 AF XY: 0.0997

Gnomad AFR exome AF: 0.0936

Gnomad AMR exome AF: 0.0517

Gnomad ASJ exome AF: 0.0923

Gnomad EAS exome AF: 0.00946

Gnomad FIN exome AF: 0.179

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0997 AC: 145745 AN: 1461410 Hom.: 7958 Cov.: 40 AF XY: 0.101 AC XY: 73110 AN XY: 727016

African (AFR) AF: 0.0977 AC: 3271 AN: 33474

American (AMR) AF: 0.0538 AC: 2404 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0962 AC: 2513 AN: 26124

East Asian (EAS) AF: 0.00582 AC: 231 AN: 39696

South Asian (SAS) AF: 0.0973 AC: 8389 AN: 86244

European-Finnish (FIN) AF: 0.176 AC: 9385 AN: 53362

Middle Eastern (MID) AF: 0.132 AC: 761 AN: 5762

European-Non Finnish (NFE) AF: 0.102 AC: 113041 AN: 1111666

Other (OTH) AF: 0.0952 AC: 5750 AN: 60376

GnomAD4 genome AF: 0.104 AC: 15762 AN: 152288 Hom.: 893 Cov.: 34 AF XY: 0.105 AC XY: 7849 AN XY: 74450

African (AFR) AF: 0.0961 AC: 3997 AN: 41572

American (AMR) AF: 0.0717 AC: 1098 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.0112 AC: 58 AN: 5188

South Asian (SAS) AF: 0.0919 AC: 444 AN: 4830

European-Finnish (FIN) AF: 0.181 AC: 1923 AN: 10604

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7588 AN: 67998

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.108 Hom.: 546

Bravo AF: 0.0940

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Fibrous dysplasia of jaw (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.78
PhyloP100		-0.12
Mutation Taster		=100/0	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: rs56323343; hg19: chr4-2822307; COSMIC: COSV62555804; COSMIC: COSV62555804;