GeneBe

rs404860

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000473562.1(NOTCH4):​n.2367A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NOTCH4
ENST00000473562.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.812

Publications

78 publications found
Variant links:
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NOTCH4NM_004557.4 linkc.1861+377A>T intron_variant Intron 11 of 29 ENST00000375023.3 NP_004548.3
NOTCH4NR_134949.2 linkn.2102+377A>T intron_variant Intron 12 of 29
NOTCH4NR_134950.2 linkn.2000+377A>T intron_variant Intron 11 of 28

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NOTCH4ENST00000473562.1 linkn.2367A>T non_coding_transcript_exon_variant Exon 11 of 11 1
NOTCH4ENST00000375023.3 linkc.1861+377A>T intron_variant Intron 11 of 29 1 NM_004557.4 ENSP00000364163.3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
187206
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
100146
African (AFR)
AF:
0.00
AC:
0
AN:
5592
American (AMR)
AF:
0.00
AC:
0
AN:
7544
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
5126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
8258
South Asian (SAS)
AF:
0.00
AC:
0
AN:
30190
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
8644
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
740
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
111322
Other (OTH)
AF:
0.00
AC:
0
AN:
9790
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.19
DANN
Benign
0.83
PhyloP100
-0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs404860; hg19: chr6-32184345; API