Genetic Variant SH3BP5:c.1151-3T>C (chr3-15256306-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004844.5(SH3BP5):c.1151-3T>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 0.00461 in 1,611,884 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 140 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 113 hom. )

Consequence

SH3BP5
NM_004844.5 splice_region, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.989

Variant links:

Genes affected

SH3BP5 (HGNC:10827): (SH3 domain binding protein 5) Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

SH3BP5 links:

SH3BP5-AS1 (HGNC:44501): (SH3BP5 antisense RNA 1)

SH3BP5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 3-15256306-A-G is Benign according to our data. Variant chr3-15256306-A-G is described in ClinVar as [Benign]. Clinvar id is 775849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP5	NM_004844.5 link	c.1151-3T>C		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000383791.8	NP_004835.2	O60239-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP5	ENST00000383791.8 link	c.1151-3T>C		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_004844.5	ENSP00000373301.3		O60239-1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3864

AN:

151364

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00971

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0173

GnomAD3 exomes

AF:

0.00642

AC:

1595

AN:

248634

Hom.:

AF XY:

0.00441

AC XY:

594

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.0867

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000261

Gnomad OTH exome

AF:

0.00229

GnomAD4 exome

AF:

0.00244

AC:

3563

AN:

1460406

Hom.:

113

Cov.:

AF XY:

0.00213

AC XY:

1544

AN XY:

726562

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.00504

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.00532

GnomAD4 genome

AF:

0.0256

AC:

3872

AN:

151478

Hom.:

140

Cov.:

AF XY:

0.0241

AC XY:

1782

AN XY:

74036

show subpopulations

Gnomad4 AFR

AF:

0.0894

Gnomad4 AMR

AF:

0.00970

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.0171

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.0293

EpiCase

AF:

0.000218

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 29, 2018

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

-0.69

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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