16-28874338-C-T

Variant names:

• chr16-28874338-C-T
• rs7359397
• NM_001387430.1:c.*518C>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.89).
• 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	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	c.*518C>T		downstream_gene_variant			NM_001387430.1	ENSP00000507475.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43257 AN: 152110 Hom.: 7963 Cov.: 33

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.: 13 AF XY: 0.292 AC XY: 63 AN XY: 216

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.: 33 AF XY: 0.284 AC XY: 21123 AN XY: 74408

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

Other links and lift over

dbSNP: rs7359397; hg19: chr16-28885659;