rs10899489

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.66
Variant links:
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]

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ACMG classification

Classification made for transcript

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
GAB2NM_080491.3 linkuse as main transcriptc.75+33319G>T intron_variant ENST00000361507.5 NP_536739.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GAB2ENST00000361507.5 linkuse as main transcriptc.75+33319G>T intron_variant 1 NM_080491.3 ENSP00000354952 P1Q9UQC2-1
ZNF75CPENST00000671814.1 linkuse as main transcriptn.120C>A non_coding_transcript_exon_variant 1/1
ENST00000672296.1 linkuse as main transcriptn.269C>A non_coding_transcript_exon_variant 1/1
ENST00000534168.1 linkuse as main transcriptn.36-59321C>A intron_variant, non_coding_transcript_variant 3

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10899489; hg19: chr11-78095373; API