chr11-20885514-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3BP4_StrongBP6_Moderate
The NM_006157.5(NELL1):c.577C>T(p.Arg193Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000406 in 1,611,494 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00050 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 2 hom. )
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
10
5
2
Clinical Significance
Conservation
PhyloP100: 4.54
Genes affected
NELL1 (HGNC:7750): (neural EGFL like 1) This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PP3
?
Multiple lines of computational evidence support a deleterious effect 8: BayesDel_addAF, BayesDel_noAF, Cadd, Dann, Eigen, MutationAssessor, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]
BP4
?
Computational evidence support a benign effect (MetaRNN=0.029604912).
BP6
?
Variant 11-20885514-C-T is Benign according to our data. Variant chr11-20885514-C-T is described in ClinVar as [Benign]. Clinvar id is 781957.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELL1 | NM_006157.5 | c.577C>T | p.Arg193Cys | missense_variant | 5/20 | ENST00000357134.10 | |
LOC105376585 | XR_931106.3 | n.194-4657G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.577C>T | p.Arg193Cys | missense_variant | 5/20 | 1 | NM_006157.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000499 AC: 76AN: 152180Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000760 AC: 191AN: 251332Hom.: 1 AF XY: 0.000758 AC XY: 103AN XY: 135838
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GnomAD4 exome AF: 0.000397 AC: 579AN: 1459196Hom.: 2 Cov.: 28 AF XY: 0.000409 AC XY: 297AN XY: 726114
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GnomAD4 genome ? AF: 0.000499 AC: 76AN: 152298Hom.: 1 Cov.: 32 AF XY: 0.000497 AC XY: 37AN XY: 74474
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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 | Jul 06, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MVP
MPC
0.54
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at