chr14-73292839-A-G
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1
The NM_001005743.2(NUMB):āc.345T>Cā(p.Ser115=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,614,244 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.015 ( 52 hom., cov: 32)
Exomes š: 0.0021 ( 72 hom. )
Consequence
NUMB
NM_001005743.2 synonymous
NM_001005743.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.629
Genes affected
NUMB (HGNC:8060): (NUMB endocytic adaptor protein) The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 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=-0.52).
BP6
Variant 14-73292839-A-G is Benign according to our data. Variant chr14-73292839-A-G is described in ClinVar as [Benign]. Clinvar id is 768663.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.629 with no splicing effect.
BA1
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NUMB | NM_001005743.2 | c.345T>C | p.Ser115= | synonymous_variant | 8/13 | ENST00000555238.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NUMB | ENST00000555238.6 | c.345T>C | p.Ser115= | synonymous_variant | 8/13 | 1 | NM_001005743.2 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0149 AC: 2276AN: 152244Hom.: 51 Cov.: 32
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GnomAD3 exomes AF: 0.00458 AC: 1152AN: 251476Hom.: 17 AF XY: 0.00367 AC XY: 499AN XY: 135914
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GnomAD4 exome AF: 0.00215 AC: 3136AN: 1461882Hom.: 72 Cov.: 30 AF XY: 0.00192 AC XY: 1398AN XY: 727242
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GnomAD4 genome AF: 0.0150 AC: 2281AN: 152362Hom.: 52 Cov.: 32 AF XY: 0.0149 AC XY: 1112AN XY: 74516
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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 | Invitae | May 30, 2018 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at