rs4788102

Positions:

• chr16-28862077-G-A

Variant summary

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

The NM_001308293.2(SH2B1):​c.-171+330G>A 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 151,972 control chromosomes in the GnomAD database, including 9,507 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 (9506 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: SH2B1 NM_001308293.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2B1	NM_001308293.2	c.-171+330G>A		intron_variant			NP_001295222.1
SH2B1	NM_001387404.1	c.-170-1591G>A		intron_variant			NP_001374333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000322610.12	c.-171+330G>A		intron_variant		2		ENSP00000321221	P3
SH2B1	ENST00000563591.5	c.-170-1591G>A		intron_variant		2		ENSP00000458097
SH2B1	ENST00000567536.5	c.-116+330G>A		intron_variant		3		ENSP00000455236

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51700 AN: 151830 Hom.: 9477 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.375 AC: 9 AN: 24 Hom.: 1 AF XY: 0.444 AC XY: 8 AN XY: 18

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.341 AC: 51793 AN: 151948 Hom.: 9506 Cov.: 32 AF XY: 0.339 AC XY: 25188 AN XY: 74250

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.310

Alfa AF: 0.373 Hom.: 14596

Bravo AF: 0.338

Asia WGS AF: 0.275 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4788102; hg19: chr16-28873398;