rs2292238
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001982.4(ERBB3):c.3129+9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,612,632 control chromosomes in the GnomAD database, including 122,710 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.33 ( 9193 hom., cov: 32)
Exomes 𝑓: 0.39 ( 113517 hom. )
Consequence
ERBB3
NM_001982.4 intron
NM_001982.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.18
Genes affected
ERBB3 (HGNC:3431): (erb-b2 receptor tyrosine kinase 3) This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 12-56100038-A-C is Benign according to our data. Variant chr12-56100038-A-C is described in ClinVar as [Benign]. Clinvar id is 1226099.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-56100038-A-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERBB3 | NM_001982.4 | c.3129+9A>C | intron_variant | ENST00000267101.8 | |||
ERBB3 | XM_047428500.1 | c.2952+9A>C | intron_variant | ||||
ERBB3 | XM_047428501.1 | c.2952+9A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERBB3 | ENST00000267101.8 | c.3129+9A>C | intron_variant | 1 | NM_001982.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.334 AC: 50818AN: 151994Hom.: 9179 Cov.: 32
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GnomAD3 exomes AF: 0.365 AC: 91819AN: 251364Hom.: 17251 AF XY: 0.365 AC XY: 49627AN XY: 135864
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GnomAD4 exome AF: 0.391 AC: 570683AN: 1460520Hom.: 113517 Cov.: 35 AF XY: 0.389 AC XY: 282694AN XY: 726604
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GnomAD4 genome ? AF: 0.334 AC: 50874AN: 152112Hom.: 9193 Cov.: 32 AF XY: 0.332 AC XY: 24718AN XY: 74366
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lethal congenital contracture syndrome 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 11, 2018 | - - |
Visceral neuropathy, familial Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at