rs2071282
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_004557.4(NOTCH4):c.611C>T(p.Pro204Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00252 in 1,613,114 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_004557.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NOTCH4 | NM_004557.4 | c.611C>T | p.Pro204Leu | missense_variant | 4/30 | ENST00000375023.3 | |
NOTCH4 | NR_134949.2 | n.750C>T | non_coding_transcript_exon_variant | 4/30 | |||
NOTCH4 | NR_134950.2 | n.750C>T | non_coding_transcript_exon_variant | 4/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOTCH4 | ENST00000375023.3 | c.611C>T | p.Pro204Leu | missense_variant | 4/30 | 1 | NM_004557.4 | P1 | |
NOTCH4 | ENST00000473562.1 | n.740C>T | non_coding_transcript_exon_variant | 4/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00231 AC: 351AN: 152236Hom.: 15 Cov.: 33
GnomAD3 exomes AF: 0.00475 AC: 1164AN: 245238Hom.: 23 AF XY: 0.00462 AC XY: 618AN XY: 133754
GnomAD4 exome AF: 0.00254 AC: 3717AN: 1460760Hom.: 138 Cov.: 45 AF XY: 0.00261 AC XY: 1898AN XY: 726698
GnomAD4 genome ? AF: 0.00232 AC: 353AN: 152354Hom.: 15 Cov.: 33 AF XY: 0.00277 AC XY: 206AN XY: 74502
ClinVar
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at