chr16-28866145-G-C

Position:

• chr16-28866145-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001387430.1(SH2B1):​c.51G>C​(p.Pro17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P17P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2B1 NM_001387430.1 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -3.02

Genes affected

SH2B1 (HGNC:30417): (SH2B adaptor protein 1) This gene encodes a member of the SH2-domain containing mediators family. The encoded protein mediates activation of various kinases and may function in cytokine and growth factor receptor signaling and cellular transformation. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-28866145-G-C is Benign according to our data. Variant chr16-28866145-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 765122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.02 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2B1	NM_001387430.1	c.51G>C	p.Pro17=	synonymous_variant	1/8	ENST00000684370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2B1	ENST00000684370.1	c.51G>C	p.Pro17=	synonymous_variant	1/8		NM_001387430.1	P3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15 AN: 127030 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.000116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000321

Gnomad EAS AF: 0.000259

Gnomad SAS AF: 0.000300

Gnomad FIN AF: 0.000267

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000102

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000804 AC: 11 AN: 136806 Hom.: 0 AF XY: 0.0000795 AC XY: 6 AN XY: 75428

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000247

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.000267

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00215 AC: 1703 AN: 792560 Hom.: 0 Cov.: 31 AF XY: 0.00211 AC XY: 841 AN XY: 397682

Gnomad4 AFR exome AF: 0.00273

Gnomad4 AMR exome AF: 0.00257

Gnomad4 ASJ exome AF: 0.00534

Gnomad4 EAS exome AF: 0.00581

Gnomad4 SAS exome AF: 0.000656

Gnomad4 FIN exome AF: 0.00441

Gnomad4 NFE exome AF: 0.00191

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000118 AC: 15 AN: 127086 Hom.: 0 Cov.: 31 AF XY: 0.0000808 AC XY: 5 AN XY: 61852

Gnomad4 AFR AF: 0.000115

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000321

Gnomad4 EAS AF: 0.000259

Gnomad4 SAS AF: 0.000300

Gnomad4 FIN AF: 0.000267

Gnomad4 NFE AF: 0.000102

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SH2B1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 03, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs751616253; hg19: chr16-28877466;