rs8055982

Positions:

• chr16-28869881-A-C
• chr16-28869881-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387430.1(SH2B1):​c.1309+498A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,126 control chromosomes in the GnomAD database, including 9,531 homozygotes. 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 0.34 (9531 hom., cov: 32)
• Consequence: SH2B1 NM_001387430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.1309+498A>C		intron_variant		ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1	c.1309+498A>C		intron_variant			NM_001387430.1	ENSP00000507475	P3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51830 AN: 152008 Hom.: 9502 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.341 AC: 51923 AN: 152126 Hom.: 9531 Cov.: 32 AF XY: 0.339 AC XY: 25244 AN XY: 74358

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.310

Alfa AF: 0.375 Hom.: 2643

Bravo AF: 0.339

Asia WGS AF: 0.275 AC: 954 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.72

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: rs8055982; hg19: chr16-28881202;