rs3744123
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_144997.7(FLCN):c.397-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 1,569,198 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_144997.7 intron
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: 0.0662 AC: 10080AN: 152184Hom.: 706 Cov.: 33
GnomAD3 exomes AF: 0.0328 AC: 5801AN: 176948Hom.: 275 AF XY: 0.0297 AC XY: 2811AN XY: 94490
GnomAD4 exome AF: 0.0282 AC: 39982AN: 1416896Hom.: 1114 Cov.: 31 AF XY: 0.0274 AC XY: 19234AN XY: 700812
GnomAD4 genome AF: 0.0663 AC: 10096AN: 152302Hom.: 706 Cov.: 33 AF XY: 0.0642 AC XY: 4783AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:6
397-13G>A in intron 5 of FLCN: This variant is not expected to have clinical sig nificance because it has been identified in 17.6% (776/4400) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs3744123). -
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not provided Benign:3
Variant summary: The FLCN c.397-13G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict that this variant abolish or weaken the normal 3' splicing donor site. However, these predictions have yet to be confirmed by functional studies. This variant is found in 1915/41366 control chromosomes (107 homozygotes) at a frequency of 0.0462941, which significantly exceeds the estimated maximal expected allele frequency of a pathogenic variant (0.0000013), suggesting this variant is benign. In addition, one clinical laboratory classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign. -
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Birt-Hogg-Dube syndrome Benign:3
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Familial spontaneous pneumothorax Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Hereditary cancer-predisposing syndrome Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at