Variant chr16-76461945-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000611870.5(CNTNAP4):c.1334-11C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,609,258 control chromosomes in the GnomAD database, including 130,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9461 hom., cov: 31)

Exomes 𝑓: 0.40 ( 120930 hom. )

Consequence

CNTNAP4
ENST00000611870.5 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.006034

Clinical Significance

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

Conservation

PhyloP100: 0.600

Variant links:

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

CNTNAP4 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=-0.76).

BP6

Variant 16-76461945-C-A is Benign according to our data. Variant chr16-76461945-C-A is described in ClinVar as [Benign]. Clinvar id is 1221600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP4	NM_033401.5 linkuse as main transcript	c.1334-11C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000611870.5	NP_207837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP4	ENST00000611870.5 linkuse as main transcript	c.1334-11C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_033401.5	ENSP00000479811	P4	Q9C0A0-1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49140

AN:

151936

Hom.:

9453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0963

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.376

AC:

94403

AN:

250784

Hom.:

19135

AF XY:

0.373

AC XY:

50578

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0871

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.387

Gnomad SAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.401

AC:

583797

AN:

1457202

Hom.:

120930

Cov.:

AF XY:

0.397

AC XY:

287759

AN XY:

725146

show subpopulations

Gnomad4 AFR exome

AF:

0.0818

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.372

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.253

Gnomad4 FIN exome

AF:

0.488

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.369

GnomAD4 genome

AF:

0.323

AC:

49163

AN:

152056

Hom.:

9461

Cov.:

AF XY:

0.327

AC XY:

24262

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0961

Gnomad4 AMR

AF:

0.402

Gnomad4 ASJ

AF:

0.343

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.486

Gnomad4 NFE

AF:

0.416

Gnomad4 OTH

AF:

0.328

Alfa

AF:

0.297

Hom.:

1286

Bravo

AF:

0.311

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	clinical testing	GeneDx	Feb 22, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.0

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0060

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.070

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