11-78268368-C-T

Position:

• chr11-78268368-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080491.3(GAB2):​c.376+12233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,928 control chromosomes in the GnomAD database, including 29,049 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 0.56 (29049 hom., cov: 31)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.376+12233G>A		intron_variant		ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.376+12233G>A		intron_variant		1	NM_080491.3	ENSP00000354952	P1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85700 AN: 151810 Hom.: 29053 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.564 AC: 85703 AN: 151928 Hom.: 29049 Cov.: 31 AF XY: 0.556 AC XY: 41264 AN XY: 74226

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.589

Alfa AF: 0.736 Hom.: 54798

Bravo AF: 0.549

Asia WGS AF: 0.301 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.012
DANN	Benign	0.68

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: rs7927923; hg19: chr11-77979414;