11-78265162-C-T

Variant names:

• chr11-78265162-C-T
• rs1981405
• NM_080491.3:c.377-14762G>A

Variant summary

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

The NM_080491.3(GAB2):​c.377-14762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 148,422 control chromosomes in the GnomAD database, including 1,715 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 0.12 (1715 hom., cov: 31)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.377-14762G>A		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.377-14762G>A		intron_variant	Intron 2 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18488 AN: 148308 Hom.: 1712 Cov.: 31

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0331

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.125 AC: 18490 AN: 148422 Hom.: 1715 Cov.: 31 AF XY: 0.131 AC XY: 9465 AN XY: 72174

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.140

Alfa AF: 0.116 Hom.: 754

Bravo AF: 0.121

Asia WGS AF: 0.236 AC: 817 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.65

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: rs1981405; hg19: chr11-77976208;