17-42682613-G-C

Position:

• chr17-42682613-G-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.-217G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 587,984 control chromosomes in the GnomAD database, including 84,705 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (19769 hom., cov: 29)
  • Exomes 𝑓: 0.54 (64936 hom.)
• Consequence: CNTNAP1 NM_003632.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.54

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 17-42682613-G-C is Benign according to our data. Variant chr17-42682613-G-C is described in ClinVar as [Benign]. Clinvar id is 1286631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTNAP1	NM_003632.3	c.-217G>C		5_prime_UTR_variant	1/24	ENST00000264638.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTNAP1	ENST00000264638.9	c.-217G>C		5_prime_UTR_variant	1/24	1	NM_003632.3	P1
CCR10	ENST00000591765.1	c.-935C>G		5_prime_UTR_variant	1/2	3
CCR10	ENST00000591568.1	c.-643+1203C>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.508 AC: 76918 AN: 151422 Hom.: 19749 Cov.: 29

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.475

GnomAD4 exome AF: 0.540 AC: 235573 AN: 436444 Hom.: 64936 Cov.: 4 AF XY: 0.545 AC XY: 125385 AN XY: 230162

Gnomad4 AFR exome AF: 0.445

Gnomad4 AMR exome AF: 0.493

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.549

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome AF: 0.508 AC: 76971 AN: 151540 Hom.: 19769 Cov.: 29 AF XY: 0.506 AC XY: 37442 AN XY: 74024

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.480

Alfa AF: 0.377 Hom.: 1052

Bravo AF: 0.496

Asia WGS AF: 0.572 AC: 1991 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	Sep 04, 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	-0.71
CADD	Benign	11
DANN	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

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: rs12947031; hg19: chr17-40834631;