16-28866166-T-C

Variant names:

• chr16-28866166-T-C
• rs1212256189
• NM_001387430.1:c.72T>C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001387430.1(SH2B1):​c.72T>C​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2B1 NM_001387430.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.09

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-6.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.72T>C	p.Pro24Pro	synonymous_variant	Exon 1 of 8	ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1	c.72T>C	p.Pro24Pro	synonymous_variant	Exon 1 of 8		NM_001387430.1	ENSP00000507475.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 124098 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.0000299

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000140

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000165 AC: 175 AN: 1061742 Hom.: 0 Cov.: 37 AF XY: 0.000161 AC XY: 84 AN XY: 522090

Gnomad4 AFR exome AF: 0.0000853

Gnomad4 AMR exome AF: 0.000198

Gnomad4 ASJ exome AF: 0.000267

Gnomad4 EAS exome AF: 0.000571

Gnomad4 SAS exome AF: 0.000435

Gnomad4 FIN exome AF: 0.000323

Gnomad4 NFE exome AF: 0.000127

Gnomad4 OTH exome AF: 0.000257

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000161 AC: 2 AN: 124136 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 1 AN XY: 60566

Gnomad4 AFR AF: 0.0000299

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000140

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00253 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1212256189; hg19: chr16-28877487;