chr17-75325960-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_002086.5(GRB2):c.237C>T(p.His79=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,614,012 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0096 ( 23 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 33 hom. )
Consequence
GRB2
NM_002086.5 synonymous
NM_002086.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.406
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 17-75325960-G-A is Benign according to our data. Variant chr17-75325960-G-A is described in ClinVar as [Benign]. Clinvar id is 778748.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.406 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00958 (1458/152236) while in subpopulation AFR AF= 0.0318 (1322/41526). AF 95% confidence interval is 0.0304. There are 23 homozygotes in gnomad4. There are 673 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1450 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRB2 | NM_002086.5 | c.237C>T | p.His79= | synonymous_variant | 4/6 | ENST00000316804.10 | |
GRB2 | NM_203506.3 | c.177-4133C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRB2 | ENST00000316804.10 | c.237C>T | p.His79= | synonymous_variant | 4/6 | 1 | NM_002086.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00953 AC: 1450AN: 152118Hom.: 23 Cov.: 32
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GnomAD3 exomes AF: 0.00250 AC: 628AN: 251486Hom.: 10 AF XY: 0.00173 AC XY: 235AN XY: 135916
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GnomAD4 exome AF: 0.00112 AC: 1642AN: 1461776Hom.: 33 Cov.: 31 AF XY: 0.00101 AC XY: 732AN XY: 727192
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GnomAD4 genome ? AF: 0.00958 AC: 1458AN: 152236Hom.: 23 Cov.: 32 AF XY: 0.00904 AC XY: 673AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at