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GeneBe

17-42683904-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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.02 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
CNTNAP1NM_003632.3 linkuse as main transcriptc.151A>C p.Arg51= synonymous_variant 2/24 ENST00000264638.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTNAP1ENST00000264638.9 linkuse as main transcriptc.151A>C p.Arg51= synonymous_variant 2/241 NM_003632.3 P1
CNTNAP1ENST00000591662.1 linkuse as main transcriptc.151A>C p.Arg51= synonymous_variant, NMD_transcript_variant 2/241
ENST00000592440.1 linkuse as main transcriptn.364-362T>G intron_variant, non_coding_transcript_variant 2
CCR10ENST00000591568.1 linkuse as main transcriptc.-731T>G 5_prime_UTR_variant 1/23

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.589
AC:
89493
AN:
151890
Hom.:
26586
Cov.:
33
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.:
50
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.589
AC:
89574
AN:
152008
Hom.:
26617
Cov.:
33
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:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
Neuropathy, congenital hypomyelinating, 3 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -
Benign, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -
Lethal congenital contracture syndrome 7 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 22, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.67
Cadd
Benign
13
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.

Other links and lift over

dbSNP: rs2271029; hg19: chr17-40835922; COSMIC: COSV52848761; COSMIC: COSV52848761; API