Genetic Variant SH2B1:c.1726-14C>T (chr16-28872520-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001387430.1(SH2B1):c.1726-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,603,166 control chromosomes in the GnomAD database, including 112,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7956 hom., cov: 32)

Exomes 𝑓: 0.37 ( 104334 hom. )

Consequence

SH2B1
NM_001387430.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0250

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 16-28872520-C-T is Benign according to our data. Variant chr16-28872520-C-T is described in ClinVar as [Benign]. Clinvar id is 1594692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1726-14C>T		intron_variant	Intron 6 of 7	ENST00000684370.1	NP_001374359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH2B1	ENST00000684370.1 link	c.1726-14C>T		intron_variant	Intron 6 of 7		NM_001387430.1	ENSP00000507475.1		Q9NRF2-1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43190

AN:

152010

Hom.:

7944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0723

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:

0.220

Gnomad NFE

AF:

0.391

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.334

AC:

82118

AN:

245952

Hom.:

16012

AF XY:

0.330

AC XY:

43748

AN XY:

132678

show subpopulations

Gnomad AFR exome

AF:

0.0660

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.0946

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.369

AC:

534765

AN:

1451038

Hom.:

104334

Cov.:

AF XY:

0.364

AC XY:

262403

AN XY:

719952

show subpopulations

Gnomad4 AFR exome

AF:

0.0557

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.124

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.421

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.284

AC:

43210

AN:

152128

Hom.:

7956

Cov.:

AF XY:

0.283

AC XY:

21078

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0721

Gnomad4 AMR

AF:

0.384

Gnomad4 ASJ

AF:

0.268

Gnomad4 EAS

AF:

0.112

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.422

Gnomad4 NFE

AF:

0.391

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.339

Hom.:

1855

Bravo

AF:

0.274

Asia WGS

AF:

0.212

AC:

735

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.49

DANN

Benign

0.42

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over