chr6-32196022-T-C
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_004557.4(NOTCH4):āc.5427A>Gā(p.Gln1809=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,598,326 control chromosomes in the GnomAD database, including 2,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.062 ( 343 hom., cov: 33)
Exomes š: 0.056 ( 2542 hom. )
Consequence
NOTCH4
NM_004557.4 synonymous
NM_004557.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.165
Genes affected
NOTCH4 (HGNC:7884): (notch receptor 4) This gene encodes a member of the NOTCH family of proteins. Members of this Type I transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple different domain types. Notch signaling is an evolutionarily conserved intercellular signaling pathway that regulates interactions between physically adjacent cells through binding of Notch family receptors to their cognate ligands. The encoded preproprotein is proteolytically processed in the trans-Golgi network to generate two polypeptide chains that heterodimerize to form the mature cell-surface receptor. This receptor may play a role in vascular, renal and hepatic development. Mutations in this gene may be associated with schizophrenia. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
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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 6-32196022-T-C is Benign according to our data. Variant chr6-32196022-T-C is described in ClinVar as [Benign]. Clinvar id is 1290716.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.165 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH4 | NM_004557.4 | c.5427A>G | p.Gln1809= | synonymous_variant | 30/30 | ENST00000375023.3 | |
NOTCH4 | NR_134949.2 | n.5135A>G | non_coding_transcript_exon_variant | 30/30 | |||
NOTCH4 | NR_134950.2 | n.5033A>G | non_coding_transcript_exon_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH4 | ENST00000375023.3 | c.5427A>G | p.Gln1809= | synonymous_variant | 30/30 | 1 | NM_004557.4 | P1 | |
NOTCH4 | ENST00000474612.1 | n.4088A>G | non_coding_transcript_exon_variant | 10/10 | 5 | ||||
NOTCH4 | ENST00000491215.1 | n.453A>G | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0616 AC: 9371AN: 152118Hom.: 345 Cov.: 33
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GnomAD3 exomes AF: 0.0531 AC: 11572AN: 217950Hom.: 409 AF XY: 0.0569 AC XY: 6906AN XY: 121402
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GnomAD4 exome AF: 0.0562 AC: 81251AN: 1446090Hom.: 2542 Cov.: 32 AF XY: 0.0571 AC XY: 41073AN XY: 719706
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GnomAD4 genome AF: 0.0615 AC: 9369AN: 152236Hom.: 343 Cov.: 33 AF XY: 0.0604 AC XY: 4499AN XY: 74436
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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 05, 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