rs775956924
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_020975.6(RET):c.626-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000016 in 1,559,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_020975.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RET | NM_020975.6 | c.626-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000355710.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RET | ENST00000355710.8 | c.626-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_020975.6 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000238 AC: 4AN: 168294Hom.: 0 AF XY: 0.0000218 AC XY: 2AN XY: 91914
GnomAD4 exome AF: 0.0000121 AC: 17AN: 1406960Hom.: 0 Cov.: 35 AF XY: 0.0000100 AC XY: 7AN XY: 696740
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74482
ClinVar
Submissions by phenotype
Multiple endocrine neoplasia, type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
RET-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 05, 2019 | 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