7-117592671-G-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_000492.4(CFTR):​c.2490+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000265 in 1,508,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CFTR
NM_000492.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.193

Publications

0 publications found
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]
CFTR Gene-Disease associations (from GenCC):
  • cystic fibrosis
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
  • congenital bilateral absence of vas deferens
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • hereditary chronic pancreatitis
    Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 7-117592671-G-A is Benign according to our data. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-117592671-G-A is described in CliVar as Likely_benign. Clinvar id is 1563155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CFTRNM_000492.4 linkc.2490+14G>A intron_variant Intron 14 of 26 ENST00000003084.11 NP_000483.3 P13569-1A0A024R730

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CFTRENST00000003084.11 linkc.2490+14G>A intron_variant Intron 14 of 26 1 NM_000492.4 ENSP00000003084.6 P13569-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000114
AC:
2
AN:
175228
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000136
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000221
AC:
3
AN:
1355762
Hom.:
0
Cov.:
31
AF XY:
0.00000150
AC XY:
1
AN XY:
667410
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
30102
American (AMR)
AF:
0.00
AC:
0
AN:
26720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20802
East Asian (EAS)
AF:
0.0000261
AC:
1
AN:
38272
South Asian (SAS)
AF:
0.00
AC:
0
AN:
62850
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48688
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5344
European-Non Finnish (NFE)
AF:
0.00000187
AC:
2
AN:
1067042
Other (OTH)
AF:
0.00
AC:
0
AN:
55942
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.023284), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.392
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74482
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
41582
American (AMR)
AF:
0.00
AC:
0
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.000193
AC:
1
AN:
5176
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10604
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68024
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

ClinVar

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

Submissions by phenotype

Cystic fibrosis Benign:1
Apr 06, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.3
DANN
Benign
0.48
PhyloP100
0.19

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs573016418; hg19: chr7-117232725; API