chr16-28872494-G-A

Position:

• chr16-28872494-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001387430.1(SH2B1):​c.1726-40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,587,946 control chromosomes in the GnomAD database, including 136 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 0.0083 (9 hom., cov: 33)
  • Exomes 𝑓: 0.012 (127 hom.)
• Consequence: SH2B1 NM_001387430.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAd4 at 1266 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.1726-40G>A		intron_variant		ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1	c.1726-40G>A		intron_variant			NM_001387430.1	ENSP00000507475	P3

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1265 AN: 152136 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00794 AC: 1852 AN: 233304 Hom.: 10 AF XY: 0.00809 AC XY: 1008 AN XY: 124644

Gnomad AFR exome AF: 0.00247

Gnomad AMR exome AF: 0.00225

Gnomad ASJ exome AF: 0.00471

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000739

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.00806

GnomAD4 exome AF: 0.0120 AC: 17190 AN: 1435694 Hom.: 127 Cov.: 32 AF XY: 0.0116 AC XY: 8239 AN XY: 710612

Gnomad4 AFR exome AF: 0.00214

Gnomad4 AMR exome AF: 0.00251

Gnomad4 ASJ exome AF: 0.00490

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000919

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.00832 AC: 1266 AN: 152252 Hom.: 9 Cov.: 33 AF XY: 0.00837 AC XY: 623 AN XY: 74460

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.0101 Hom.: 4

Bravo AF: 0.00708

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.9
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs62037368; hg19: chr16-28883815;