chr11-95813062-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014679.5(CEP57):āc.333G>Cā(p.Gln111His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 1,613,574 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_014679.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00601 AC: 915AN: 152172Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00562 AC: 1411AN: 251034Hom.: 11 AF XY: 0.00570 AC XY: 774AN XY: 135744
GnomAD4 exome AF: 0.00661 AC: 9663AN: 1461284Hom.: 46 Cov.: 32 AF XY: 0.00649 AC XY: 4721AN XY: 726962
GnomAD4 genome AF: 0.00601 AC: 916AN: 152290Hom.: 6 Cov.: 32 AF XY: 0.00611 AC XY: 455AN XY: 74476
ClinVar
Submissions by phenotype
not provided Benign:2
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CEP57: BS2 -
not specified Benign:1
The CEP57 p.Gln102His variant was identified in the literature in 1 of 96 Italian patients with gastric or lobular breast cancers (Tedaldi_2019_PMID:31514334). The variant was identified in dbSNP (ID: rs117321017) and ClinVar (classified as benign by Invitae), but was not identified in LOVD 3.0 or Cosmic. The variant was identified in control databases in 1635 of 282426 chromosomes (12 homozygous) at a frequency of 0.005789 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 1135 of 128908 chromosomes (freq: 0.008805), Other in 53 of 7198 chromosomes (freq: 0.007363), European (Finnish) in 167 of 25120 chromosomes (freq: 0.006648), Ashkenazi Jewish in 62 of 10366 chromosomes (freq: 0.005981), Latino in 104 of 35428 chromosomes (freq: 0.002936), South Asian in 76 of 30602 chromosomes (freq: 0.002483) and African in 38 of 24856 chromosomes (freq: 0.001529), but was not observed in the East Asian population. The p.Gln102 residue is conserved in mammals but not in more distantly related organisms however four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. -
Mosaic variegated aneuploidy syndrome 2 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at