4-2820435-G-A

Variant names:

• chr4-2820435-G-A
• rs231401
• NM_001122681.2:c.-4-179G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001122681.2(SH3BP2):​c.-4-179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,108 control chromosomes in the GnomAD database, including 3,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (3095 hom., cov: 32)
• Consequence: SH3BP2 NM_001122681.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.406
• 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), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-2820435-G-A is Benign according to our data. Variant chr4-2820435-G-A is described in ClinVar as [Benign]. Clinvar id is 1222999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP2	NM_001122681.2	c.-4-179G>A		intron_variant	Intron 1 of 12	ENST00000503393.8	NP_001116153.1
SH3BP2	NM_001145856.2	c.168-179G>A		intron_variant	Intron 1 of 12		NP_001139328.1
SH3BP2	NM_001145855.2	c.81-179G>A		intron_variant	Intron 1 of 12		NP_001139327.1
SH3BP2	NM_003023.4	c.-4-179G>A		intron_variant	Intron 1 of 12		NP_003014.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP2	ENST00000503393.8	c.-4-179G>A		intron_variant	Intron 1 of 12	1	NM_001122681.2	ENSP00000422168.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24768 AN: 151990 Hom.: 3085 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.0938

Gnomad FIN AF: 0.0411

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.163 AC: 24811 AN: 152108 Hom.: 3095 Cov.: 32 AF XY: 0.157 AC XY: 11664 AN XY: 74384

African (AFR) AF: 0.352 AC: 14604 AN: 41436

American (AMR) AF: 0.118 AC: 1802 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3472

East Asian (EAS) AF: 0.00772 AC: 40 AN: 5184

South Asian (SAS) AF: 0.0920 AC: 444 AN: 4824

European-Finnish (FIN) AF: 0.0411 AC: 436 AN: 10614

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0969 AC: 6588 AN: 67982

Other (OTH) AF: 0.154 AC: 325 AN: 2104

Alfa AF: 0.129 Hom.: 667

Bravo AF: 0.176

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.64
PhyloP100		-0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs231401; hg19: chr4-2822162;