Variant 3-3040078-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_175607.3(CNTN4):c.2205T>C(p.Tyr735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,614,206 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 11 hom., cov: 34)

Exomes 𝑓: 0.00057 ( 9 hom. )

Consequence

CNTN4
NM_175607.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.838

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 3-3040078-T-C is Benign according to our data. Variant chr3-3040078-T-C is described in ClinVar as [Benign]. Clinvar id is 790523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00503 (767/152396) while in subpopulation AFR AF= 0.0175 (726/41602). AF 95% confidence interval is 0.0164. There are 11 homozygotes in gnomad4. There are 353 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 767 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN4	NM_175607.3 linkuse as main transcript	c.2205T>C	p.Tyr735=	synonymous_variant	20/25	ENST00000418658.6	NP_783200.1
CNTN4-AS1	NR_046554.1 linkuse as main transcript	n.595A>G		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN4	ENST00000418658.6 linkuse as main transcript	c.2205T>C	p.Tyr735=	synonymous_variant	20/25	5	NM_175607.3	ENSP00000396010	P1	Q8IWV2-1

Frequencies

GnomAD3 genomes

AF:

0.00497

AC:

757

AN:

152278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00140

AC:

351

AN:

251436

Hom.:

AF XY:

0.00102

AC XY:

139

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000569

AC:

832

AN:

1461810

Hom.:

Cov.:

AF XY:

0.000465

AC XY:

338

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00503

AC:

767

AN:

152396

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.0175

Gnomad4 AMR

AF:

0.00202

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00606

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

2.6

DANN

Benign

0.64

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

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