rs4151648
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000063.6(C2):c.2200C>T(p.Arg734Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000894 in 1,613,048 control chromosomes in the GnomAD database, including 11 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. R734L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000063.6 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 |
---|---|---|---|---|---|---|---|
C2 | NM_000063.6 | c.2200C>T | p.Arg734Cys | missense_variant | 18/18 | ENST00000299367.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C2 | ENST00000299367.10 | c.2200C>T | p.Arg734Cys | missense_variant | 18/18 | 1 | NM_000063.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00432 AC: 658AN: 152178Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00178 AC: 439AN: 246592Hom.: 3 AF XY: 0.00150 AC XY: 202AN XY: 134416
GnomAD4 exome AF: 0.000536 AC: 783AN: 1460752Hom.: 5 Cov.: 32 AF XY: 0.000457 AC XY: 332AN XY: 726686
GnomAD4 genome AF: 0.00433 AC: 659AN: 152296Hom.: 6 Cov.: 32 AF XY: 0.00414 AC XY: 308AN XY: 74472
ClinVar
Submissions by phenotype
Complement component 2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Age related macular degeneration 14 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 13, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at