17-42683801-A-AT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003632.3(CNTNAP1):c.68-20_68-19insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,606,512 control chromosomes in the GnomAD database, including 293,054 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24373 hom., cov: 0)
  • Exomes 𝑓: 0.61 (268681 hom.)
• Consequence: CNTNAP1 NM_003632.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.676

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]

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-42683801-A-AT is Benign according to our data. Variant chr17-42683801-A-AT is described in ClinVar as [Benign]. Clinvar id is 1167004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP1	NM_003632.3	c.68-20_68-19insT		intron_variant		ENST00000264638.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP1	ENST00000264638.9	c.68-20_68-19insT		intron_variant		1	NM_003632.3	P1
CNTNAP1	ENST00000591662.1	c.68-20_68-19insT		intron_variant, NMD_transcript_variant		1
	ENST00000592440.1	n.364-260_364-259insA		intron_variant, non_coding_transcript_variant		2
CCR10	ENST00000591568.1	c.-643+14_-643+15insA		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85368 AN: 151728 Hom.: 24348 Cov.: 0

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.533

GnomAD3 exomes AF: 0.582 AC: 140996 AN: 242430 Hom.: 41650 AF XY: 0.589 AC XY: 77593 AN XY: 131806

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.455

Gnomad SAS exome AF: 0.681

Gnomad FIN exome AF: 0.632

Gnomad NFE exome AF: 0.606

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.605 AC: 880581 AN: 1454666 Hom.: 268681 Cov.: 38 AF XY: 0.607 AC XY: 439348 AN XY: 723876

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.538

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.679

Gnomad4 FIN exome AF: 0.636

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.563 AC: 85429 AN: 151846 Hom.: 24373 Cov.: 0 AF XY: 0.562 AC XY: 41714 AN XY: 74188

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.537

Alfa AF: 0.557 Hom.: 4395

Bravo AF: 0.546

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs36108420; hg19: chr17-40835819;