chr7-117711772-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_033427.3(CTTNBP2):c.4757C>T(p.Pro1586Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00534 in 1,611,120 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0054 ( 45 hom. )

Consequence

CTTNBP2
NM_033427.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.56

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]

CTTNBP2 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056162477).

BP6

Variant 7-117711772-G-A is Benign according to our data. Variant chr7-117711772-G-A is described in ClinVar as [Benign]. Clinvar id is 2657962.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTTNBP2	NM_033427.3 link	c.4757C>T	p.Pro1586Leu	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
CTTNBP2	ENST00000160373.8 link	c.4757C>T	p.Pro1586Leu	missense_variant	Exon 23 of 23	1	NM_033427.3	ENSP00000160373.3		Q8WZ74

Frequencies

GnomAD3 genomes

AF:

0.00472

AC:

718

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0224

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00565

AC:

1400

AN:

247748

Hom.:

AF XY:

0.00568

AC XY:

761

AN XY:

134074

show subpopulations

Gnomad AFR exome

AF:

0.000803

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00172

Gnomad FIN exome

AF:

0.0243

Gnomad NFE exome

AF:

0.00667

Gnomad OTH exome

AF:

0.00413

GnomAD4 exome

AF:

0.00540

AC:

7883

AN:

1458920

Hom.:

Cov.:

AF XY:

0.00533

AC XY:

3865

AN XY:

725362

show subpopulations

Gnomad4 AFR exome

AF:

0.000749

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.000499

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00166

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.00550

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00472

AC:

718

AN:

152200

Hom.:

Cov.:

AF XY:

0.00518

AC XY:

385

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0224

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00537

Hom.:

Bravo

AF:

0.00283

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00523

AC:

ExAC

AF:

0.00538

AC:

653

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00509

EpiControl

AF:

0.00486

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CTTNBP2-related disorder

Benign:1

Jul 01, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CTTNBP2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0056

MetaSVM

Uncertain

-0.095

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.26

MVP

0.89

MPC

0.49

ClinPred

0.025

GERP RS

5.9

Varity_R

0.10

gMVP

0.24

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over