6-32195940-C-T
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004557.4(NOTCH4):c.5509G>A(p.Ala1837Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000798 in 1,590,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_004557.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NOTCH4 | NM_004557.4 | c.5509G>A | p.Ala1837Thr | missense_variant | 30/30 | ENST00000375023.3 | NP_004548.3 | |
NOTCH4 | NR_134949.2 | n.5217G>A | non_coding_transcript_exon_variant | 30/30 | ||||
NOTCH4 | NR_134950.2 | n.5115G>A | non_coding_transcript_exon_variant | 29/29 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NOTCH4 | ENST00000375023.3 | c.5509G>A | p.Ala1837Thr | missense_variant | 30/30 | 1 | NM_004557.4 | ENSP00000364163.3 | ||
NOTCH4 | ENST00000474612.1 | n.4170G>A | non_coding_transcript_exon_variant | 10/10 | 5 | |||||
NOTCH4 | ENST00000491215.1 | n.535G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000302 AC: 46AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000116 AC: 24AN: 207448Hom.: 0 AF XY: 0.000121 AC XY: 14AN XY: 115800
GnomAD4 exome AF: 0.0000563 AC: 81AN: 1438394Hom.: 0 Cov.: 32 AF XY: 0.0000531 AC XY: 38AN XY: 715268
GnomAD4 genome AF: 0.000302 AC: 46AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74378
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2024 | The c.5509G>A (p.A1837T) alteration is located in exon 30 (coding exon 30) of the NOTCH4 gene. This alteration results from a G to A substitution at nucleotide position 5509, causing the alanine (A) at amino acid position 1837 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at