Genetic Variant SH2B1:c.*518C>T (chr16-28874338-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387430.1(SH2B1):c.*518C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 152,592 control chromosomes in the GnomAD database, including 7,988 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 0.28 ( 7975 hom., cov: 33)

Exomes 𝑓: 0.28 ( 13 hom. )

Consequence

SH2B1
NM_001387430.1 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.29

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2B1	NM_001387430.1 link	c.*518C>T		downstream_gene_variant		ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1 link	c.*518C>T		downstream_gene_variant			NM_001387430.1	ENSP00000507475.1		Q9NRF2-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43257

AN:

152110

Hom.:

7963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0724

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.422

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.277

AC:

101

AN:

364

Hom.:

AF XY:

0.292

AC XY:

AN XY:

216

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.429

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.250

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.429

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.188

GnomAD4 genome

AF:

0.284

AC:

43278

AN:

152228

Hom.:

7975

Cov.:

AF XY:

0.284

AC XY:

21123

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0722

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.356

Hom.:

12138

Bravo

AF:

0.274

Asia WGS

AF:

0.212

AC:

736

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

DANN

Benign

0.44

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over