NM_080491.3:c.75+55201C>T

Variant names:

• chr11-78362445-G-A
• rs11603112
• NM_080491.3:c.75+55201C>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.75+55201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 151,546 control chromosomes in the GnomAD database, including 5,659 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 0.26 (5659 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 14 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]

ENSG00000288853 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAB2	NM_080491.3	c.75+55201C>T		intron_variant	Intron 1 of 9	ENST00000361507.5	NP_536739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.75+55201C>T		intron_variant	Intron 1 of 9	1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38826 AN: 151428 Hom.: 5643 Cov.: 32

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.257 AC: 38881 AN: 151546 Hom.: 5659 Cov.: 32 AF XY: 0.260 AC XY: 19254 AN XY: 74022

African (AFR) AF: 0.379 AC: 15673 AN: 41354

American (AMR) AF: 0.280 AC: 4254 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1034 AN: 3462

East Asian (EAS) AF: 0.413 AC: 2120 AN: 5132

South Asian (SAS) AF: 0.301 AC: 1447 AN: 4814

European-Finnish (FIN) AF: 0.204 AC: 2134 AN: 10478

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.169 AC: 11489 AN: 67792

Other (OTH) AF: 0.259 AC: 545 AN: 2102

Alfa AF: 0.202 Hom.: 1807

Bravo AF: 0.267

Asia WGS AF: 0.300 AC: 1036 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		0.094
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: rs11603112; hg19: chr11-78073491;