rs6413464
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2
The NM_000077.5(CDKN2A):c.379G>T(p.Ala127Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,610,798 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000077.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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CDKN2A | ENST00000304494.10 | c.379G>T | p.Ala127Ser | missense_variant | Exon 2 of 3 | 1 | NM_000077.5 | ENSP00000307101.5 | ||
CDKN2A | ENST00000579755 | c.*23G>T | 3_prime_UTR_variant | Exon 2 of 3 | 1 | NM_058195.4 | ENSP00000462950.1 |
Frequencies
GnomAD3 genomes AF: 0.00487 AC: 741AN: 152236Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00129 AC: 316AN: 244500Hom.: 0 AF XY: 0.000991 AC XY: 132AN XY: 133184
GnomAD4 exome AF: 0.000541 AC: 789AN: 1458444Hom.: 7 Cov.: 31 AF XY: 0.000445 AC XY: 323AN XY: 725684
GnomAD4 genome AF: 0.00488 AC: 743AN: 152354Hom.: 6 Cov.: 32 AF XY: 0.00444 AC XY: 331AN XY: 74506
ClinVar
Submissions by phenotype
not provided Benign:5
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This variant is associated with the following publications: (PMID: 26650189, 28944238, 18983535, 25780468, 7970734, 26104880, 22703879, 22995991, 25064638, 15860862, 20981092, 24728327, 9823374, 19141585, 26775776, 7777061, 10498896, 21462282, 12485439, 29552713, 20505745, 18573309) -
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not specified Benign:4Other:1
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Hereditary cancer-predisposing syndrome Benign:4
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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. -
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Melanoma-pancreatic cancer syndrome Benign:2
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Melanoma and neural system tumor syndrome;C1835044:Melanoma, cutaneous malignant, susceptibility to, 2;C1838547:Melanoma-pancreatic cancer syndrome Benign:1
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Melanoma, cutaneous malignant, susceptibility to, 2 Benign:1
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Familial melanoma Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at