Genetic Variant SH3BP1:c.103-7T>C (chr22-37641367-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018957.6(SH3BP1):c.103-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,551,126 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 102 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 111 hom. )

Consequence

SH3BP1
NM_018957.6 splice_region, intron

Scores

Splicing: ADA: 0.00001710

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.803

Variant links:

Genes affected

SH3BP1 (HGNC:10824): (SH3 domain binding protein 1) This gene encodes a member of the Rho GTPase activating protein (RhoGAP) family. The encoded protein regulates Rac signaling and plays a role in cytoskeletal dynamics, cell motility and epithelial junction formation. This protein's association with the exocyst complex, which tethers secretory vesicles to the plasma membrane, has been demonstrated to be important in cell motility. In a distinct complex, this protein has been shown to regulate epithelial junction formation and morphogenesis. By interacting with the Plexin-D1 cell surface receptor, this protein mediates changes in the cytoskeleton in response to semaphorin binding. This protein may promote metastasis in human liver cancer cells and tissues. [provided by RefSeq, Mar 2017]

SH3BP1 links:

ENSG00000285304 (HGNC:):

ENSG00000285304 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 22-37641367-T-C is Benign according to our data. Variant chr22-37641367-T-C is described in ClinVar as [Benign]. Clinvar id is 780656.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP1	NM_018957.6 link	c.103-7T>C		splice_region_variant, intron_variant	Intron 2 of 17	ENST00000649765.2	NP_061830.3	Q9Y3L3-1A0A2X0SFX7
SH3BP1	NM_001350055.2 link	c.103-7T>C		splice_region_variant, intron_variant	Intron 2 of 17		NP_001336984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP1	ENST00000649765.2 link	c.103-7T>C		splice_region_variant, intron_variant	Intron 2 of 17		NM_018957.6	ENSP00000497104.1		Q9Y3L3-1
ENSG00000285304	ENST00000451997.6 link	c.-90-7T>C		splice_region_variant, intron_variant	Intron 1 of 16	2		ENSP00000401076.2		F8WEQ3

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2947

AN:

152190

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0679

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00464

AC:

720

AN:

155328

Hom.:

AF XY:

0.00351

AC XY:

288

AN XY:

81944

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.00271

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000218

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00199

AC:

2778

AN:

1398818

Hom.:

111

Cov.:

AF XY:

0.00169

AC XY:

1169

AN XY:

689958

show subpopulations

Gnomad4 AFR exome

AF:

0.0742

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000519

Gnomad4 OTH exome

AF:

0.00421

GnomAD4 genome

AF:

0.0193

AC:

2947

AN:

152308

Hom.:

102

Cov.:

AF XY:

0.0191

AC XY:

1425

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0677

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.0220

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 11, 2017

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.75

CADD

Benign

1.7

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.016

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over