Genetic Variant CNTN4:c.2511+41A>G (chr3-3042463-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_175607.3(CNTN4):c.2511+41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,268,916 control chromosomes in the GnomAD database, including 17,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4913 hom., cov: 32)

Exomes 𝑓: 0.14 ( 12933 hom. )

Consequence

CNTN4
NM_175607.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

CNTN4 (HGNC:2174): (contactin 4) This gene encodes a member of the contactin family of immunoglobulins. Contactins are axon-associated cell adhesion molecules that function in neuronal network formation and plasticity. The encoded protein is a glycosylphosphatidylinositol-anchored neuronal membrane protein that may play a role in the formation of axon connections in the developing nervous system. Deletion or mutation of this gene may play a role in 3p deletion syndrome and autism spectrum disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

CNTN4 links:

CNTN4-AS1 (HGNC:39985): (CNTN4 antisense RNA 1)

CNTN4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-3042463-A-G is Benign according to our data. Variant chr3-3042463-A-G is described in ClinVar as [Benign]. Clinvar id is 1177914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN4	NM_175607.3 link	c.2511+41A>G		intron_variant	Intron 21 of 24	ENST00000418658.6	NP_783200.1	Q8IWV2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6 link	c.2511+41A>G		intron_variant	Intron 21 of 24	5	NM_175607.3	ENSP00000396010.1		Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32958

AN:

151940

Hom.:

4898

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0948

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.204

GnomAD3 exomes

AF:

0.154

AC:

37397

AN:

243620

Hom.:

3689

AF XY:

0.148

AC XY:

19474

AN XY:

131636

show subpopulations

Gnomad AFR exome

AF:

0.444

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.202

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0957

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.141

AC:

157579

AN:

1116858

Hom.:

12933

Cov.:

AF XY:

0.140

AC XY:

79882

AN XY:

572480

show subpopulations

Gnomad4 AFR exome

AF:

0.436

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.177

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0930

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.217

AC:

33012

AN:

152058

Hom.:

4913

Cov.:

AF XY:

0.212

AC XY:

15747

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.159

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0948

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.166

Hom.:

1457

Bravo

AF:

0.233

Asia WGS

AF:

0.143

AC:

499

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.014

DANN

Benign

0.36

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