rs62037369

Variant names:

• chr16-28872520-C-T
• rs62037369
• NM_001387430.1:c.1726-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-28872520-C-T
• chr16-28872520-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency

  Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387430.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	NM_001387430.1	MANE Select	c.1726-14C>T		intron	N/A	NP_001374359.1	Q9NRF2-1
	SH2B1	NM_001145795.2		c.1726-14C>T		intron	N/A	NP_001139267.1	Q9NRF2-1
	SH2B1	NM_001308293.2		c.1726-14C>T		intron	N/A	NP_001295222.1	Q9NRF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH2B1	ENST00000684370.1	MANE Select	c.1726-14C>T		intron	N/A	ENSP00000507475.1	Q9NRF2-1
	SH2B1	ENST00000618521.4	TSL:1	c.1726-14C>T		intron	N/A	ENSP00000481709.1	Q9NRF2-1
	SH2B1	ENST00000359285.10	TSL:1	c.1726-14C>T		intron	N/A	ENSP00000352232.5	Q9NRF2-3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43190 AN: 152010 Hom.: 7944 Cov.: 32

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

GnomAD2 exomes AF: 0.334 AC: 82118 AN: 245952 AF XY: 0.330

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 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.: 36 AF XY: 0.364 AC XY: 262403 AN XY: 719952

African (AFR) AF: 0.0557 AC: 1856 AN: 33330

American (AMR) AF: 0.480 AC: 21307 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 6920 AN: 25554

East Asian (EAS) AF: 0.124 AC: 4888 AN: 39484

South Asian (SAS) AF: 0.214 AC: 18217 AN: 85096

European-Finnish (FIN) AF: 0.421 AC: 22373 AN: 53088

Middle Eastern (MID) AF: 0.197 AC: 1130 AN: 5726

European-Non Finnish (NFE) AF: 0.397 AC: 438372 AN: 1104472

Other (OTH) AF: 0.329 AC: 19702 AN: 59876

GnomAD4 genome AF: 0.284 AC: 43210 AN: 152128 Hom.: 7956 Cov.: 32 AF XY: 0.283 AC XY: 21078 AN XY: 74362

African (AFR) AF: 0.0721 AC: 2993 AN: 41528

American (AMR) AF: 0.384 AC: 5866 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 929 AN: 3472

East Asian (EAS) AF: 0.112 AC: 580 AN: 5176

South Asian (SAS) AF: 0.201 AC: 971 AN: 4826

European-Finnish (FIN) AF: 0.422 AC: 4468 AN: 10580

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26544 AN: 67952

Other (OTH) AF: 0.272 AC: 574 AN: 2110

Alfa AF: 0.339 Hom.: 1855

Bravo AF: 0.274

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.49
DANN	Benign	0.42
PhyloP100		-0.025
PromoterAI		-0.037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62037369; hg19: chr16-28883841; COSMIC: COSV59468091; COSMIC: COSV59468091;