17-42683596-A-C

Position:

• chr17-42683596-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003632.3(CNTNAP1):​c.68-225A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00643 in 1,403,222 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (169 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (134 hom.)
• Consequence: CNTNAP1 NM_003632.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.615

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-42683596-A-C is Benign according to our data. Variant chr17-42683596-A-C is described in ClinVar as [Benign]. Clinvar id is 1183884.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP1	NM_003632.3	c.68-225A>C		intron_variant		ENST00000264638.9	NP_003623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTNAP1	ENST00000264638.9	c.68-225A>C		intron_variant		1	NM_003632.3	ENSP00000264638	P1
CNTNAP1	ENST00000591662.1	c.68-225A>C		intron_variant, NMD_transcript_variant		1		ENSP00000466571
	ENST00000592440.1	n.364-54T>G		intron_variant, non_coding_transcript_variant		2
CCR10	ENST00000591568.1	c.-643+220T>G		intron_variant		3		ENSP00000467331

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3979 AN: 152016 Hom.: 169 Cov.: 33

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00402 AC: 5024 AN: 1251088 Hom.: 134 Cov.: 33 AF XY: 0.00377 AC XY: 2277 AN XY: 604248

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.0122

Gnomad4 ASJ exome AF: 0.00848

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000173

Gnomad4 FIN exome AF: 0.0000726

Gnomad4 NFE exome AF: 0.00149

Gnomad4 OTH exome AF: 0.00928

GnomAD4 genome AF: 0.0263 AC: 3999 AN: 152134 Hom.: 169 Cov.: 33 AF XY: 0.0252 AC XY: 1877 AN XY: 74368

Gnomad4 AFR AF: 0.0849

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0201 Hom.: 12

Bravo AF: 0.0313

Asia WGS AF: 0.00693 AC: 24 AN: 3478

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	Jul 31, 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	-0.73
CADD	Benign	8.8
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8075349; hg19: chr17-40835614;