16-28865303-G-T

Variant names:

• chr16-28865303-G-T
• rs561051168
• NM_001387430.1:c.-792G>T

Variant summary

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

The NM_001387430.1(SH2B1):​c.-792G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000096 in 833,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: SH2B1 NM_001387430.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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=-0.92).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH2B1	NM_001387430.1	c.-792G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000684370.1	NP_001374359.1
SH2B1	NM_001387430.1	c.-792G>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370	c.-792G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8		NM_001387430.1	ENSP00000507475.1
SH2B1	ENST00000684370	c.-792G>T		5_prime_UTR_variant	Exon 1 of 8		NM_001387430.1	ENSP00000507475.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000960 AC: 8 AN: 833320 Hom.: 0 Cov.: 30 AF XY: 0.0000130 AC XY: 5 AN XY: 384832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000105

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.60

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: rs561051168; hg19: chr16-28876624;