rs756872302

Variant names:

• chr16-28866167-A-C
• rs756872302
• NM_001387430.1:c.73A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-28866167-A-C
• chr16-28866167-A-G
• chr16-28866167-A-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001387430.1(SH2B1):​c.73A>C​(p.Ser25Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S25C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SH2B1 NM_001387430.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.47
• Publications: 0 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: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.296206).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	NM_001387430.1	MANE Select	c.73A>C	p.Ser25Arg	missense	Exon 1 of 8	NP_001374359.1	Q9NRF2-1
	SH2B1	NM_001145795.2		c.73A>C	p.Ser25Arg	missense	Exon 2 of 9	NP_001139267.1	Q9NRF2-1
	SH2B1	NM_001308293.2		c.73A>C	p.Ser25Arg	missense	Exon 4 of 11	NP_001295222.1	Q9NRF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	ENST00000684370.1	MANE Select	c.73A>C	p.Ser25Arg	missense	Exon 1 of 8	ENSP00000507475.1	Q9NRF2-1
	SH2B1	ENST00000618521.4	TSL:1	c.73A>C	p.Ser25Arg	missense	Exon 2 of 9	ENSP00000481709.1	Q9NRF2-1
	SH2B1	ENST00000359285.10	TSL:1	c.73A>C	p.Ser25Arg	missense	Exon 2 of 10	ENSP00000352232.5	Q9NRF2-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 146148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1385586 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 684778

African (AFR) AF: 0.00 AC: 0 AN: 31450

American (AMR) AF: 0.00 AC: 0 AN: 35884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24450

East Asian (EAS) AF: 0.00 AC: 0 AN: 35514

South Asian (SAS) AF: 0.00 AC: 0 AN: 79142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4430

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074360

Other (OTH) AF: 0.00 AC: 0 AN: 56946

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 146148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 71160

African (AFR) AF: 0.00 AC: 0 AN: 39244

American (AMR) AF: 0.00 AC: 0 AN: 14786

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.00 AC: 0 AN: 4870

South Asian (SAS) AF: 0.00 AC: 0 AN: 4528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66208

Other (OTH) AF: 0.00 AC: 0 AN: 2036

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PhyloP100		4.5
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.12
Sift	Uncertain	0.029	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.17	B
Vest4		0.61
MutPred		0.49		Loss of phosphorylation at S25 (P = 0.0041)
MVP		0.10
MPC		0.91
ClinPred		0.92	D
GERP RS		2.5
PromoterAI		0.043	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs756872302; hg19: chr16-28877488;