chr17-42683631-T-C

Position:

• chr17-42683631-T-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.68-190T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 1,425,788 control chromosomes in the GnomAD database, including 261,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24477 hom., cov: 31)
  • Exomes 𝑓: 0.61 (237133 hom.)
• Consequence: CNTNAP1 NM_003632.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.282

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=-0.75).
• BP6: Variant 17-42683631-T-C is Benign according to our data. Variant chr17-42683631-T-C is described in ClinVar as [Benign]. Clinvar id is 1283421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTNAP1	NM_003632.3	c.68-190T>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.68-190T>C		intron_variant		1	NM_003632.3	ENSP00000264638	P1
CNTNAP1	ENST00000591662.1	c.68-190T>C		intron_variant, NMD_transcript_variant		1		ENSP00000466571
	ENST00000592440.1	n.364-89A>G		intron_variant, non_coding_transcript_variant		2
CCR10	ENST00000591568.1	c.-643+185A>G		intron_variant		3		ENSP00000467331

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85526 AN: 151742 Hom.: 24451 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.534

GnomAD4 exome AF: 0.608 AC: 774379 AN: 1273926 Hom.: 237133 Cov.: 37 AF XY: 0.609 AC XY: 376132 AN XY: 617126

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.461

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.639

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.586

GnomAD4 genome AF: 0.564 AC: 85588 AN: 151862 Hom.: 24477 Cov.: 31 AF XY: 0.564 AC XY: 41845 AN XY: 74238

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.537

Alfa AF: 0.577 Hom.: 24804

Bravo AF: 0.547

Asia WGS AF: 0.613 AC: 2136 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4028634; hg19: chr17-40835649; COSMIC: COSV52853619; COSMIC: COSV52853619;