chr11-78285357-C-A

Variant names:

• chr11-78285357-C-A
• rs10793294
• NM_080491.3:c.76-4456G>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.76-4456G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,120 control chromosomes in the GnomAD database, including 31,623 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 0.62 (31623 hom., cov: 33)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 27 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=-0.64).
• 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 rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-4456G>T		intron_variant	Intron 1 of 9	ENST00000361507.5	NP_536739.1
GAB2	NM_012296.4	c.-39-4456G>T		intron_variant	Intron 1 of 9		NP_036428.1
GAB2	XM_024448782.2	c.22-4456G>T		intron_variant	Intron 1 of 9		XP_024304550.1
GAB2	XM_047427935.1	c.-39-4456G>T		intron_variant	Intron 1 of 9		XP_047283891.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-4456G>T		intron_variant	Intron 1 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94015 AN: 152002 Hom.: 31628 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.892

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.618 AC: 94030 AN: 152120 Hom.: 31623 Cov.: 33 AF XY: 0.607 AC XY: 45135 AN XY: 74376

African (AFR) AF: 0.399 AC: 16571 AN: 41482

American (AMR) AF: 0.626 AC: 9568 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2265 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1200 AN: 5164

South Asian (SAS) AF: 0.421 AC: 2027 AN: 4818

European-Finnish (FIN) AF: 0.639 AC: 6766 AN: 10584

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53299 AN: 68004

Other (OTH) AF: 0.630 AC: 1331 AN: 2114

Alfa AF: 0.720 Hom.: 110444

Bravo AF: 0.610

Asia WGS AF: 0.322 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	10
DANN	Benign	0.85
PhyloP100		0.069
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: rs10793294; hg19: chr11-77996403;