rs6723461
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005235.3(ERBB4):c.234+67C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,557,234 control chromosomes in the GnomAD database, including 2,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.071 ( 681 hom., cov: 32)
Exomes 𝑓: 0.039 ( 1534 hom. )
Consequence
ERBB4
NM_005235.3 intron
NM_005235.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0560
Genes affected
ERBB4 (HGNC:3432): (erb-b2 receptor tyrosine kinase 4) This gene is a member of the Tyr protein kinase family and the epidermal growth factor receptor subfamily. It encodes a single-pass type I membrane protein with multiple cysteine rich domains, a transmembrane domain, a tyrosine kinase domain, a phosphotidylinositol-3 kinase binding site and a PDZ domain binding motif. The protein binds to and is activated by neuregulins and other factors and induces a variety of cellular responses including mitogenesis and differentiation. Multiple proteolytic events allow for the release of a cytoplasmic fragment and an extracellular fragment. Mutations in this gene have been associated with cancer. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 2-212124685-G-C is Benign according to our data. Variant chr2-212124685-G-C is described in ClinVar as [Benign]. Clinvar id is 1239508.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERBB4 | NM_005235.3 | c.234+67C>G | intron_variant | ENST00000342788.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERBB4 | ENST00000342788.9 | c.234+67C>G | intron_variant | 1 | NM_005235.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0712 AC: 10826AN: 152074Hom.: 681 Cov.: 32
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GnomAD4 exome AF: 0.0391 AC: 54923AN: 1405042Hom.: 1534 Cov.: 23 AF XY: 0.0385 AC XY: 27064AN XY: 702166
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GnomAD4 genome AF: 0.0712 AC: 10841AN: 152192Hom.: 681 Cov.: 32 AF XY: 0.0697 AC XY: 5188AN XY: 74432
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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 | GeneDx | May 13, 2021 | - - |
Computational scores
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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