rs200545007
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001164507.2(NEB):c.4834C>T(p.Arg1612Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000464 in 1,613,854 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1612H) has been classified as Likely benign.
Frequency
Consequence
NM_001164507.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.4834C>T | p.Arg1612Cys | missense_variant | 41/182 | ENST00000427231.7 | |
NEB | NM_001164508.2 | c.4834C>T | p.Arg1612Cys | missense_variant | 41/182 | ENST00000397345.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.4834C>T | p.Arg1612Cys | missense_variant | 41/182 | 5 | NM_001164508.2 | P5 | |
NEB | ENST00000427231.7 | c.4834C>T | p.Arg1612Cys | missense_variant | 41/182 | 5 | NM_001164507.2 | A2 | |
NEB | ENST00000409198.5 | c.4834C>T | p.Arg1612Cys | missense_variant | 41/150 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00126 AC: 191AN: 152070Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000618 AC: 154AN: 249142Hom.: 0 AF XY: 0.000503 AC XY: 68AN XY: 135144
GnomAD4 exome AF: 0.000380 AC: 556AN: 1461666Hom.: 0 Cov.: 31 AF XY: 0.000344 AC XY: 250AN XY: 727120
GnomAD4 genome ? AF: 0.00127 AC: 193AN: 152188Hom.: 3 Cov.: 32 AF XY: 0.00140 AC XY: 104AN XY: 74408
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 31, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | May 16, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 16, 2020 | This variant is associated with the following publications: (PMID: 23887774, 23167750) - |
Nemaline myopathy 2 Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2021 | The c.4834C>T (p.R1612C) alteration is located in exon 41 (coding exon 39) of the NEB gene. This alteration results from a C to T substitution at nucleotide position 4834, causing the arginine (R) at amino acid position 1612 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
NEB-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 14, 2021 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at