7-117559652-A-G
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000492.4(CFTR):c.1581A>G(p.Glu527Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000843 in 1,611,220 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000492.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CFTR | NM_000492.4 | c.1581A>G | p.Glu527Glu | synonymous_variant | Exon 11 of 27 | ENST00000003084.11 | NP_000483.3 | |
CFTR-AS1 | NR_149084.1 | n.221+1081T>C | intron_variant | Intron 2 of 2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00444 AC: 676AN: 152166Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00118 AC: 296AN: 250744Hom.: 1 AF XY: 0.000907 AC XY: 123AN XY: 135622
GnomAD4 exome AF: 0.000467 AC: 682AN: 1458936Hom.: 6 Cov.: 30 AF XY: 0.000402 AC XY: 292AN XY: 726024
GnomAD4 genome AF: 0.00444 AC: 676AN: 152284Hom.: 6 Cov.: 32 AF XY: 0.00423 AC XY: 315AN XY: 74462
ClinVar
Submissions by phenotype
Cystic fibrosis Benign:3
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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. -
not provided Benign:3
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not specified Benign:2
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Glu527Glu in exon 11 of CFTR: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.9% (82/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1800094). -
CFTR-related disorder Benign:2
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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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Hereditary pancreatitis Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at