7-117610555-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP6_Moderate

The NM_000492.4(CFTR):​c.3025G>T​(p.Ala1009Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CFTR
NM_000492.4 missense

Scores

1
5
13

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.92
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 2 ACMG points.

PM1
In a domain ABC transmembrane type-1 2 (size 296) in uniprot entity CFTR_HUMAN there are 53 pathogenic changes around while only 8 benign (87%) in NM_000492.4
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 7-117610555-G-T is Benign according to our data. Variant chr7-117610555-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2447415.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFTRNM_000492.4 linkc.3025G>T p.Ala1009Ser missense_variant Exon 19 of 27 ENST00000003084.11 NP_000483.3 P13569-1A0A024R730

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFTRENST00000003084.11 linkc.3025G>T p.Ala1009Ser missense_variant Exon 19 of 27 1 NM_000492.4 ENSP00000003084.6 P13569-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cystic fibrosis Benign:1
Mar 08, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
15
DANN
Uncertain
0.97
DEOGEN2
Uncertain
0.46
T;.;.;T;.
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.39
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.75
T;T;T;T;T
M_CAP
Pathogenic
0.57
D
MetaRNN
Uncertain
0.50
T;T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-0.92
N;.;.;.;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.71
N;.;.;N;.
REVEL
Uncertain
0.39
Sift
Benign
1.0
T;.;.;T;.
Sift4G
Benign
1.0
T;.;.;T;.
Polyphen
0.0
B;.;.;.;.
Vest4
0.35
MutPred
0.71
Gain of glycosylation at A1009 (P = 0.049);.;.;.;.;
MVP
0.96
MPC
0.0043
ClinPred
0.82
D
GERP RS
4.9
Varity_R
0.35
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs184724618; hg19: chr7-117250609; API