17-42683904-A-C

Position:

chr17-42683904-A-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003632.3(CNTNAP1):c.151A>C(p.Arg51=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,613,058 control chromosomes in the GnomAD database, including 300,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26617 hom., cov: 33)

Exomes 𝑓: 0.61 ( 273632 hom. )

Consequence

CNTNAP1
NM_003632.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.02

Variant links:

Genes affected

CNTNAP1 (HGNC:8011): (contactin associated protein 1) The gene product was initially identified as a 190-kD protein associated with the contactin-PTPRZ1 complex. The 1,384-amino acid protein, also designated p190 or CASPR for 'contactin-associated protein,' includes an extracellular domain with several putative protein-protein interaction domains, a putative transmembrane domain, and a 74-amino acid cytoplasmic domain. Northern blot analysis showed that the gene is transcribed predominantly in brain as a transcript of 6.2 kb, with weak expression in several other tissues tested. The architecture of its extracellular domain is similar to that of neurexins, and this protein may be the signaling subunit of contactin, enabling recruitment and activation of intracellular signaling pathways in neurons. [provided by RefSeq, Jan 2009]

CNTNAP1 links:

(HGNC:):

links:

CCR10 (HGNC:4474): (C-C motif chemokine receptor 10) Chemokines are a group of small (approximately 8 to 14 kD), mostly basic, structurally related molecules that regulate cell trafficking of various types of leukocytes through interactions with a subset of 7-transmembrane, G protein-coupled receptors. Chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis. Chemokines are divided into 2 major subfamilies, CXC and CC, based on the arrangement of the first 2 of the 4 conserved cysteine residues; the 2 cysteines are separated by a single amino acid in CXC chemokines and are adjacent in CC chemokines. CCR10 is the receptor for CCL27 (SCYA27; MIM 604833); CCR10-CCL27 interactions are involved in T cell-mediated skin inflammation (Homey et al., 2002 [PubMed 11821900]).[supplied by OMIM, Mar 2008]

CCR10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 17-42683904-A-C is Benign according to our data. Variant chr17-42683904-A-C is described in ClinVar as [Benign]. Clinvar id is 803394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.02 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP1	NM_003632.3 linkuse as main transcript	c.151A>C	p.Arg51=	synonymous_variant	2/24	ENST00000264638.9	NP_003623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CNTNAP1	ENST00000264638.9 linkuse as main transcript	c.151A>C	p.Arg51=	synonymous_variant	2/24	1	NM_003632.3	ENSP00000264638	P1
CNTNAP1	ENST00000591662.1 linkuse as main transcript	c.151A>C	p.Arg51=	synonymous_variant, NMD_transcript_variant	2/24	1		ENSP00000466571
	ENST00000592440.1 linkuse as main transcript	n.364-362T>G		intron_variant, non_coding_transcript_variant		2
CCR10	ENST00000591568.1 linkuse as main transcript	c.-731T>G		5_prime_UTR_variant	1/2	3		ENSP00000467331

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89493

AN:

151890

Hom.:

26586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.593

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.446

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.680

Gnomad FIN

AF:

0.633

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.568

GnomAD3 exomes

AF:

0.591

AC:

147986

AN:

250198

Hom.:

44469

AF XY:

0.596

AC XY:

80681

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.590

Gnomad AMR exome

AF:

0.547

Gnomad ASJ exome

AF:

0.452

Gnomad EAS exome

AF:

0.455

Gnomad SAS exome

AF:

0.682

Gnomad FIN exome

AF:

0.633

Gnomad NFE exome

AF:

0.609

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.610

AC:

891158

AN:

1461050

Hom.:

273632

Cov.:

AF XY:

0.611

AC XY:

444227

AN XY:

726866

show subpopulations

Gnomad4 AFR exome

AF:

0.592

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.461

Gnomad4 SAS exome

AF:

0.679

Gnomad4 FIN exome

AF:

0.638

Gnomad4 NFE exome

AF:

0.617

Gnomad4 OTH exome

AF:

0.594

GnomAD4 genome

AF:

0.589

AC:

89574

AN:

152008

Hom.:

26617

Cov.:

AF XY:

0.588

AC XY:

43675

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.593

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.446

Gnomad4 EAS

AF:

0.457

Gnomad4 SAS

AF:

0.679

Gnomad4 FIN

AF:

0.633

Gnomad4 NFE

AF:

0.607

Gnomad4 OTH

AF:

0.571

Alfa

AF:

0.583

Hom.:

31970

Bravo

AF:

0.579

Asia WGS

AF:

0.615

AC:

2143

AN:

3478

EpiCase

AF:

0.587

EpiControl

AF:

0.582

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Neuropathy, congenital hypomyelinating, 3

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -

Lethal congenital contracture syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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