7-117711658-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033427.3(CTTNBP2):​c.4871C>A​(p.Ser1624Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CTTNBP2
NM_033427.3 missense

Scores

4
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79
Variant links:
Genes affected
CTTNBP2 (HGNC:15679): (cortactin binding protein 2) This gene encodes a protein with six ankyrin repeats and several proline-rich regions. A similar gene in rat interacts with a central regulator of the actin cytoskeleton. [provided by RefSeq, Jul 2008]
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25695312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTTNBP2NM_033427.3 linkc.4871C>A p.Ser1624Tyr missense_variant Exon 23 of 23 ENST00000160373.8 NP_219499.1 Q8WZ74Q20BG9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTTNBP2ENST00000160373.8 linkc.4871C>A p.Ser1624Tyr missense_variant Exon 23 of 23 1 NM_033427.3 ENSP00000160373.3 Q8WZ74

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251216
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461774
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727184
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.20
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.26
T
MetaSVM
Uncertain
-0.024
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-1.3
N
REVEL
Uncertain
0.31
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.010
D
Polyphen
0.99
D
Vest4
0.32
MutPred
0.21
Gain of methylation at K1628 (P = 0.0495);
MVP
0.88
MPC
0.50
ClinPred
0.76
D
GERP RS
5.9
Varity_R
0.12
gMVP
0.21

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

LitVar

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

Other links and lift over

dbSNP: rs370798516; hg19: chr7-117351712; API