Variant 7-117719610-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033427.3(CTTNBP2):c.4538C>T(p.Thr1513Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CTTNBP2
NM_033427.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.623

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:

LOC105375469 (HGNC:):

LOC105375469 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04707083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTTNBP2	NM_033427.3 linkuse as main transcript	c.4538C>T	p.Thr1513Met	missense_variant	21/23	ENST00000160373.8
LOC105375469	XR_927902.3 linkuse as main transcript	n.89+3639G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CTTNBP2	ENST00000160373.8 linkuse as main transcript	c.4538C>T	p.Thr1513Met	missense_variant	21/23	1	NM_033427.3	P1
CTTNBP2	ENST00000446636.5 linkuse as main transcript	c.3002C>T	p.Thr1001Met	missense_variant	19/21	5
CTTNBP2	ENST00000441556.5 linkuse as main transcript	c.*2452C>T		3_prime_UTR_variant, NMD_transcript_variant	21/23	5
CTTNBP2	ENST00000445366.1 linkuse as main transcript	c.*255C>T		3_prime_UTR_variant, NMD_transcript_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000757

AC:

AN:

250996

Hom.:

AF XY:

0.0000811

AC XY:

AN XY:

135666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461222

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2021

The c.4538C>T (p.T1513M) alteration is located in exon 21 (coding exon 21) of the CTTNBP2 gene. This alteration results from a C to T substitution at nucleotide position 4538, causing the threonine (T) at amino acid position 1513 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.42

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.042

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.73

M_CAP

Benign

0.019

MetaRNN

Benign

0.047

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.1

REVEL

Benign

0.073

Sift

Benign

0.13

Sift4G

Benign

0.14

Polyphen

0.046

Vest4

0.18

MutPred

0.17

Gain of helix (P = 0.0696);

MVP

0.41

MPC

0.096

ClinPred

0.023

GERP RS

-0.98

Varity_R

0.019

gMVP

0.17

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.

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