rs10899489

Positions:

• chr11-78384327-C-A
• chr11-78384327-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.75+33319G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,106 control chromosomes in the GnomAD database, including 4,651 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 0.23 (4651 hom., cov: 32)
• Consequence: GAB2 NM_080491.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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]

ZNF75CP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAB2	NM_080491.3	c.75+33319G>T		intron_variant		ENST00000361507.5	NP_536739.1
ZNF75CP		n.78384327C>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAB2	ENST00000361507.5	c.75+33319G>T		intron_variant		1	NM_080491.3	ENSP00000354952.4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35389 AN: 151988 Hom.: 4630 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.233 AC: 35459 AN: 152106 Hom.: 4651 Cov.: 32 AF XY: 0.237 AC XY: 17605 AN XY: 74352

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.279

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.242

Alfa AF: 0.161 Hom.: 710

Bravo AF: 0.243

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.51

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: rs10899489; hg19: chr11-78095373;