11-78279214-G-A

Variant names:

• chr11-78279214-G-A
• rs4945261
• NM_080491.3:c.376+1387C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080491.3(GAB2):​c.376+1387C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,124 control chromosomes in the GnomAD database, including 2,437 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 0.16 (2437 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 35 publications found

Genes affected

GAB2 (HGNC:14458): (GRB2 associated binding protein 2) This gene is a member of the GRB2-associated binding protein (GAB) gene family. These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. Two alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.376+1387C>T		intron_variant	Intron 2 of 9	ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.376+1387C>T		intron_variant	Intron 2 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23916 AN: 152006 Hom.: 2435 Cov.: 32

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.157 AC: 23931 AN: 152124 Hom.: 2437 Cov.: 32 AF XY: 0.163 AC XY: 12096 AN XY: 74368

African (AFR) AF: 0.0612 AC: 2540 AN: 41520

American (AMR) AF: 0.237 AC: 3625 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3464

East Asian (EAS) AF: 0.404 AC: 2087 AN: 5170

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4814

European-Finnish (FIN) AF: 0.201 AC: 2129 AN: 10576

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10969 AN: 67980

Other (OTH) AF: 0.174 AC: 368 AN: 2110

Alfa AF: 0.169 Hom.: 1479

Bravo AF: 0.156

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.41
PhyloP100		1.1
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: rs4945261; hg19: chr11-77990260;