rs1800076
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_000492.4(CFTR):c.224G>A(p.Arg75Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 1,611,610 control chromosomes in the GnomAD database, including 1,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000492.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CFTR | NM_000492.4 | c.224G>A | p.Arg75Gln | missense_variant | Exon 3 of 27 | ENST00000003084.11 | NP_000483.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0186 AC: 2830AN: 152172Hom.: 44 Cov.: 33
GnomAD3 exomes AF: 0.0154 AC: 3874AN: 250966Hom.: 59 AF XY: 0.0153 AC XY: 2080AN XY: 135648
GnomAD4 exome AF: 0.0313 AC: 45647AN: 1459320Hom.: 999 Cov.: 29 AF XY: 0.0299 AC XY: 21694AN XY: 726240
GnomAD4 genome AF: 0.0186 AC: 2830AN: 152290Hom.: 44 Cov.: 33 AF XY: 0.0159 AC XY: 1183AN XY: 74466
ClinVar
Submissions by phenotype
Cystic fibrosis Uncertain:2Benign:6
the variant does not result in CFTR-RD neither -
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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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not specified Benign:5
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not provided Uncertain:1Benign:3
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CFTR: BS1, BS2 -
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CFTR-related disorder Uncertain:1Benign:1
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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:1Other:1
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Lung disease, non-specific Uncertain:1
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Abnormality of the pancreas Other:1
Variant interpretted as Uncertain significance and reported on 02-10-2019 by Lab or GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at