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GeneBe

rs4542691

Variant summary

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

The NM_002086.5(GRB2):c.176+1816A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,044 control chromosomes in the GnomAD database, including 31,928 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 0.60 ( 31928 hom., cov: 30)

Consequence

GRB2
NM_002086.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59
Variant links:
Genes affected
GRB2 (HGNC:4566): (growth factor receptor bound protein 2) The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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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=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GRB2NM_002086.5 linkuse as main transcriptc.176+1816A>G intron_variant ENST00000316804.10
GRB2NM_203506.3 linkuse as main transcriptc.176+1816A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GRB2ENST00000316804.10 linkuse as main transcriptc.176+1816A>G intron_variant 1 NM_002086.5 P1P62993-1

Frequencies

GnomAD3 genomes
AF:
0.601
AC:
91376
AN:
151926
Hom.:
31941
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.221
Gnomad AMI
AF:
0.776
Gnomad AMR
AF:
0.682
Gnomad ASJ
AF:
0.567
Gnomad EAS
AF:
0.866
Gnomad SAS
AF:
0.679
Gnomad FIN
AF:
0.832
Gnomad MID
AF:
0.532
Gnomad NFE
AF:
0.753
Gnomad OTH
AF:
0.590
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.601
AC:
91368
AN:
152044
Hom.:
31928
Cov.:
30
AF XY:
0.610
AC XY:
45296
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.220
Gnomad4 AMR
AF:
0.682
Gnomad4 ASJ
AF:
0.567
Gnomad4 EAS
AF:
0.866
Gnomad4 SAS
AF:
0.679
Gnomad4 FIN
AF:
0.832
Gnomad4 NFE
AF:
0.753
Gnomad4 OTH
AF:
0.587
Alfa
AF:
0.715
Hom.:
52481
Bravo
AF:
0.576
Asia WGS
AF:
0.676
AC:
2352
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
Cadd
Benign
0.072
Dann
Benign
0.38

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: rs4542691; hg19: chr17-73326965; API