Genetic Variant CNTN5:c.277+10A>G (chr11-99819775-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_014361.4(CNTN5):c.277+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0070 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0041 ( 0 hom. )

Consequence

CNTN5
NM_014361.4 intron

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.495

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-99819775-A-G is Benign according to our data. Variant chr11-99819775-A-G is described in ClinVar as [Benign]. Clinvar id is 3054065.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4 link	c.277+10A>G		intron_variant	Intron 4 of 24	ENST00000524871.6	NP_055176.1	O94779-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6 link	c.277+10A>G		intron_variant	Intron 4 of 24	1	NM_014361.4	ENSP00000435637.1		O94779-1

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

AN:

9480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.00382

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0420

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0118

AC:

133

AN:

11318

AF XY:

0.0115

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.183

Gnomad EAS exome

AF:

0.00206

Gnomad FIN exome

AF:

0.0471

Gnomad NFE exome

AF:

0.00895

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00408

AC:

457

AN:

112034

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

234

AN XY:

54982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2652

American (AMR)

AF:

0.00

AC:

AN:

5980

Ashkenazi Jewish (ASJ)

AF:

0.106

AC:

154

AN:

1452

East Asian (EAS)

AF:

0.00141

AC:

AN:

9196

South Asian (SAS)

AF:

0.00361

AC:

AN:

9140

European-Finnish (FIN)

AF:

0.0419

AC:

148

AN:

3532

Middle Eastern (MID)

AF:

0.00197

AC:

AN:

508

European-Non Finnish (NFE)

AF:

0.00104

AC:

AN:

75136

Other (OTH)

AF:

0.00676

AC:

AN:

4438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00704

AC:

AN:

9520

Hom.:

Cov.:

AF XY:

0.00915

AC XY:

AN XY:

5028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2406

American (AMR)

AF:

0.00

AC:

AN:

1642

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

AN:

146

East Asian (EAS)

AF:

0.00382

AC:

AN:

1310

South Asian (SAS)

AF:

0.00

AC:

AN:

568

European-Finnish (FIN)

AF:

0.0420

AC:

AN:

858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00245

AC:

AN:

2452

Other (OTH)

AF:

0.00

AC:

AN:

112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000898

Hom.:

Bravo

AF:

0.000234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CNTN5-related disorder

Benign:1

May 21, 2020

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.49

PromoterAI

0.035

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

11-99819775-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over