Variant 11-99819697-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014361.4(CNTN5):c.209T>G(p.Leu70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.49 ( 0 hom., cov: 54)

Exomes 𝑓: 0.48 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

CNTN5
NM_014361.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.847

Variant links:

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CNTN5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017924607).

BP6

Variant 11-99819697-T-G is Benign according to our data. Variant chr11-99819697-T-G is described in ClinVar as [Benign]. Clinvar id is 768471.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4 linkuse as main transcript	c.209T>G	p.Leu70Arg	missense_variant	4/25	ENST00000524871.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6 linkuse as main transcript	c.209T>G	p.Leu70Arg	missense_variant	4/25	1	NM_014361.4	P1	O94779-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

72605

AN:

149464

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.500

Gnomad AMR

AF:

0.466

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.470

Gnomad FIN

AF:

0.485

Gnomad MID

AF:

0.490

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.489

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.485

AC:

643618

AN:

1328178

Hom.:

Cov.:

AF XY:

0.485

AC XY:

322173

AN XY:

664450

show subpopulations

Gnomad4 AFR exome

AF:

0.484

Gnomad4 AMR exome

AF:

0.448

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.490

Gnomad4 OTH exome

AF:

0.485

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.486

AC:

72654

AN:

149574

Hom.:

Cov.:

AF XY:

0.484

AC XY:

35340

AN XY:

73004

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.466

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.406

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.485

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.186

Hom.:

ExAC

AF:

0.475

AC:

57043

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 14, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.10

.;T;T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.084

LIST_S2

Benign

0.20

T;.;T;T

MetaRNN

Benign

0.0018

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.8

N;N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.39

N;N;N;.

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

0.35

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.20

MPC

0.045

ClinPred

0.0041

GERP RS

3.1

Varity_R

0.055

gMVP

0.31

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