rs8055982

Variant names:

• chr16-28869881-A-C
• rs8055982
• NM_001387430.1:c.1309+498A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

SH2B1 Gene-Disease associations (from GenCC):

• severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.1309+498A>C		intron_variant	Intron 4 of 7	ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1	c.1309+498A>C		intron_variant	Intron 4 of 7		NM_001387430.1	ENSP00000507475.1

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

African (AFR) AF: 0.265 AC: 11011 AN: 41506

American (AMR) AF: 0.406 AC: 6208 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 930 AN: 3472

East Asian (EAS) AF: 0.120 AC: 623 AN: 5182

South Asian (SAS) AF: 0.217 AC: 1048 AN: 4820

European-Finnish (FIN) AF: 0.423 AC: 4464 AN: 10560

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26696 AN: 67976

Other (OTH) AF: 0.310 AC: 654 AN: 2108

Alfa AF: 0.373 Hom.: 2666

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
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8055982; hg19: chr16-28881202;