Menu
GeneBe

rs1800100

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_000492.4(CFTR):c.2002C>A(p.Arg668Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R668C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CFTR
NM_000492.4 missense

Scores

7
10
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52
Variant links:
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 Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr7-117592169-C-T is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.753

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFTRNM_000492.4 linkuse as main transcriptc.2002C>A p.Arg668Ser missense_variant 14/27 ENST00000003084.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFTRENST00000003084.11 linkuse as main transcriptc.2002C>A p.Arg668Ser missense_variant 14/271 NM_000492.4 P2P13569-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;.;T;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Pathogenic
0.75
D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.4
M;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.5
N;.;N;.
REVEL
Pathogenic
0.70
Sift
Uncertain
0.0030
D;.;D;.
Sift4G
Pathogenic
0.0
D;.;D;.
Polyphen
1.0
D;.;.;.
Vest4
0.75
MutPred
0.37
Gain of disorder (P = 0.086);.;.;.;
MVP
1.0
MPC
0.0055
ClinPred
0.95
D
GERP RS
4.5
Varity_R
0.90
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1800100; hg19: chr7-117232223; API