chr16-28872006-T-C

Position:

• chr16-28872006-T-C

Variant summary

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

The NM_001387430.1(SH2B1):​c.1513+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 1,489,392 control chromosomes in the GnomAD database, including 331,705 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 0.68 (35327 hom., cov: 30)
  • Exomes 𝑓: 0.66 (296378 hom.)
• Consequence: SH2B1 NM_001387430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.838 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH2B1	NM_001387430.1	c.1513+23T>C		intron_variant		ENST00000684370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH2B1	ENST00000684370.1	c.1513+23T>C		intron_variant			NM_001387430.1	P3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103018 AN: 151776 Hom.: 35264 Cov.: 30

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.654

GnomAD3 exomes AF: 0.691 AC: 170918 AN: 247440 Hom.: 60208 AF XY: 0.692 AC XY: 92715 AN XY: 134034

Gnomad AFR exome AF: 0.742

Gnomad AMR exome AF: 0.789

Gnomad ASJ exome AF: 0.593

Gnomad EAS exome AF: 0.716

Gnomad SAS exome AF: 0.855

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.638

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.662 AC: 885498 AN: 1337498 Hom.: 296378 Cov.: 22 AF XY: 0.667 AC XY: 448406 AN XY: 672028

Gnomad4 AFR exome AF: 0.741

Gnomad4 AMR exome AF: 0.787

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.670

GnomAD4 genome AF: 0.679 AC: 103141 AN: 151894 Hom.: 35327 Cov.: 30 AF XY: 0.681 AC XY: 50540 AN XY: 74214

Gnomad4 AFR AF: 0.738

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.712

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.658

Alfa AF: 0.652 Hom.: 8262

Bravo AF: 0.689

Asia WGS AF: 0.818 AC: 2839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.5
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs28433345; hg19: chr16-28883327; COSMIC: COSV59466153; COSMIC: COSV59466153;