4-2824745-G-T

Variant names:

• chr4-2824745-G-T
• rs62620003
• NM_001122681.2:c.357+15G>T

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.357+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0437 in 1,573,094 control chromosomes in the GnomAD database, including 1,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (223 hom., cov: 34)
  • Exomes 𝑓: 0.043 (1561 hom.)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.520
• 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: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-2824745-G-T is Benign according to our data. Variant chr4-2824745-G-T is described in ClinVar as Benign. ClinVar VariationId is 258895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0844 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.357+15G>T		intron	N/A	NP_001116153.1	A0A384N6E5
	SH3BP2	NM_001145856.2		c.528+15G>T		intron	N/A	NP_001139328.1	P78314-4
	SH3BP2	NM_001145855.2		c.441+15G>T		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.357+15G>T		intron	N/A	ENSP00000422168.3	P78314-1
	SH3BP2	ENST00000511747.6	TSL:1	c.528+15G>T		intron	N/A	ENSP00000424846.2	P78314-4
	SH3BP2	ENST00000356331.10	TSL:1	n.618+15G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0487 AC: 7412 AN: 152162 Hom.: 223 Cov.: 34

Gnomad AFR AF: 0.0727

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.0272

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0483

GnomAD2 exomes AF: 0.0456 AC: 11360 AN: 249006 AF XY: 0.0475

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.0481

Gnomad ASJ exome AF: 0.0473

Gnomad EAS exome AF: 0.0289

Gnomad FIN exome AF: 0.00422

Gnomad NFE exome AF: 0.0384

Gnomad OTH exome AF: 0.0457

GnomAD4 exome AF: 0.0431 AC: 61295 AN: 1420814 Hom.: 1561 Cov.: 26 AF XY: 0.0446 AC XY: 31613 AN XY: 709408

African (AFR) AF: 0.0803 AC: 2628 AN: 32712

American (AMR) AF: 0.0479 AC: 2138 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 1245 AN: 25908

East Asian (EAS) AF: 0.0287 AC: 1134 AN: 39510

South Asian (SAS) AF: 0.0912 AC: 7796 AN: 85514

European-Finnish (FIN) AF: 0.00540 AC: 282 AN: 52222

Middle Eastern (MID) AF: 0.0803 AC: 456 AN: 5682

European-Non Finnish (NFE) AF: 0.0399 AC: 42893 AN: 1075556

Other (OTH) AF: 0.0461 AC: 2723 AN: 59058

GnomAD4 genome AF: 0.0487 AC: 7415 AN: 152280 Hom.: 223 Cov.: 34 AF XY: 0.0492 AC XY: 3662 AN XY: 74472

African (AFR) AF: 0.0726 AC: 3017 AN: 41546

American (AMR) AF: 0.0518 AC: 792 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3472

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5176

South Asian (SAS) AF: 0.0915 AC: 442 AN: 4832

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0384 AC: 2612 AN: 68006

Other (OTH) AF: 0.0478 AC: 101 AN: 2114

Alfa AF: 0.0207 Hom.: 8

Bravo AF: 0.0520

Asia WGS AF: 0.0520 AC: 184 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.60
PhyloP100		-0.52
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.3
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: rs62620003; hg19: chr4-2826472;