rs11978434
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000492.4(CFTR):c.1767-136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 571,422 control chromosomes in the GnomAD database, including 14,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.20 ( 3563 hom., cov: 32)
Exomes 𝑓: 0.22 ( 11346 hom. )
Consequence
CFTR
NM_000492.4 intron
NM_000492.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.167
Genes affected
CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 7-117591798-T-C is Benign according to our data. Variant chr7-117591798-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1177029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117591798-T-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CFTR | NM_000492.4 | c.1767-136T>C | intron_variant | ENST00000003084.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CFTR | ENST00000003084.11 | c.1767-136T>C | intron_variant | 1 | NM_000492.4 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.203 AC: 30776AN: 151948Hom.: 3561 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
30776
AN:
151948
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.217 AC: 91110AN: 419356Hom.: 11346 AF XY: 0.213 AC XY: 46921AN XY: 220250
GnomAD4 exome
AF:
AC:
91110
AN:
419356
Hom.:
AF XY:
AC XY:
46921
AN XY:
220250
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.203 AC: 30795AN: 152066Hom.: 3563 Cov.: 32 AF XY: 0.205 AC XY: 15226AN XY: 74334
GnomAD4 genome
?
AF:
AC:
30795
AN:
152066
Hom.:
Cov.:
32
AF XY:
AC XY:
15226
AN XY:
74334
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
302
AN:
3458
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 22, 2023 | Variant summary: CFTR c.1767-136T>C is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.23 in 31304 control chromosomes in the gnomAD database, including 993 homozygotes. The observed variant frequency is approximately 17.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in CFTR causing Cystic Fibrosis phenotype (0.013), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1767-136T>C in individuals affected with Cystic Fibrosis and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. - |
Cystic fibrosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 01, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 21, 2018 | - - |
CFTR-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 13, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at