rs10899489

Variant names:

• chr11-78384327-C-A
• rs10899489
• NM_080491.3:c.75+33319G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-78384327-C-A
• chr11-78384327-C-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+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
• Publications: 51 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]

ZNF75CP (HGNC:13148): (zinc finger protein 75C, pseudogene) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000293272 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080491.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	NM_080491.3	MANE Select	c.75+33319G>T		intron	N/A	NP_536739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAB2	ENST00000361507.5	TSL:1 MANE Select	c.75+33319G>T		intron	N/A	ENSP00000354952.4
	ZNF75CP	ENST00000671814.1		n.120C>A		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000293272	ENST00000672296.1		n.269C>A		non_coding_transcript_exon	Exon 1 of 1

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

African (AFR) AF: 0.314 AC: 13032 AN: 41498

American (AMR) AF: 0.274 AC: 4183 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 966 AN: 3466

East Asian (EAS) AF: 0.404 AC: 2082 AN: 5154

South Asian (SAS) AF: 0.297 AC: 1433 AN: 4818

European-Finnish (FIN) AF: 0.178 AC: 1878 AN: 10578

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11189 AN: 68008

Other (OTH) AF: 0.242 AC: 510 AN: 2104

Alfa AF: 0.165 Hom.: 781

Bravo AF: 0.243

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.51
PhyloP100		-1.7
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: rs10899489; hg19: chr11-78095373;