12-11869562-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001987.5(ETV6):āc.602T>Cā(p.Leu201Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,613,942 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_001987.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ETV6 | NM_001987.5 | c.602T>C | p.Leu201Pro | missense_variant | 5/8 | ENST00000396373.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ETV6 | ENST00000396373.9 | c.602T>C | p.Leu201Pro | missense_variant | 5/8 | 1 | NM_001987.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00489 AC: 743AN: 151956Hom.: 1 Cov.: 31
GnomAD3 exomes AF: 0.00494 AC: 1243AN: 251426Hom.: 5 AF XY: 0.00489 AC XY: 664AN XY: 135886
GnomAD4 exome AF: 0.00731 AC: 10684AN: 1461868Hom.: 49 Cov.: 31 AF XY: 0.00714 AC XY: 5191AN XY: 727238
GnomAD4 genome AF: 0.00489 AC: 744AN: 152074Hom.: 1 Cov.: 31 AF XY: 0.00469 AC XY: 349AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | ETV6: BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2022 | See Variant Classification Assertion Criteria. - |
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The ETV6 p.Leu201Pro variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs145477191) and ClinVar (classified as benign by Genetic Services Laboratory, University of Chicago). The variant was also identified in control databases in 1409 of 282794 chromosomes (6 homozygous) at a frequency of 0.004982 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 1077 of 129130 chromosomes (freq: 0.00834), Other in 36 of 7224 chromosomes (freq: 0.004983), Latino in 163 of 35438 chromosomes (freq: 0.0046), African in 43 of 24960 chromosomes (freq: 0.001723), European (Finnish) in 40 of 25112 chromosomes (freq: 0.001593), South Asian in 41 of 30616 chromosomes (freq: 0.001339) and Ashkenazi Jewish in 9 of 10368 chromosomes (freq: 0.000868), while the variant was not observed in the East Asian population. The p.Leu201 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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 the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 22, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at