11-78303011-G-T

Position:

• chr11-78303011-G-T

Variant summary

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

The NM_080491.3(GAB2):​c.76-22110C>A 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 152,144 control chromosomes in the GnomAD database, including 2,416 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 (2416 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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]

LOC105369402 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.76-22110C>A		intron_variant		ENST00000361507.5	NP_536739.1
LOC105369402	XR_950343.4	n.322+5926G>T		intron_variant, non_coding_transcript_variant
GAB2	NM_012296.4	c.-39-22110C>A		intron_variant			NP_036428.1
GAB2	XM_024448782.2	c.22-22110C>A		intron_variant			XP_024304550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.76-22110C>A		intron_variant		1	NM_080491.3	ENSP00000354952	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23806 AN: 152026 Hom.: 2414 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.157 AC: 23821 AN: 152144 Hom.: 2416 Cov.: 32 AF XY: 0.162 AC XY: 12037 AN XY: 74372

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.173

Alfa AF: 0.174 Hom.: 428

Bravo AF: 0.155

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	-0.76
CADD	Benign	1.2
DANN	Benign	0.82

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: rs10899467; hg19: chr11-78014057;