chr17-42683904-A-C

Variant names:

• chr17-42683904-A-C
• rs2271029
• NM_003632.3:c.151A>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003632.3(CNTNAP1):​c.151A>C​(p.Arg51Arg) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.02
• Publications: 36 publications found

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]

ENSG00000267765 (HGNC:58591):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-42683904-A-C is Benign according to our data. Variant chr17-42683904-A-C is described in ClinVar as Benign. ClinVar VariationId is 803394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003632.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP1	NM_003632.3	MANE Select	c.151A>C	p.Arg51Arg	synonymous	Exon 2 of 24	NP_003623.1	P78357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP1	ENST00000264638.9	TSL:1 MANE Select	c.151A>C	p.Arg51Arg	synonymous	Exon 2 of 24	ENSP00000264638.3	P78357
	CNTNAP1	ENST00000591662.1	TSL:1	n.151A>C		non_coding_transcript_exon	Exon 2 of 24	ENSP00000466571.1	K7EMM9
	CCR10	ENST00000591568.1	TSL:3	c.-731T>G		5_prime_UTR	Exon 1 of 2	ENSP00000467331.1	K7EPC9

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89493 AN: 151890 Hom.: 26586 Cov.: 33

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

GnomAD2 exomes AF: 0.591 AC: 147986 AN: 250198 AF XY: 0.596

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 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

African (AFR) AF: 0.592 AC: 19825 AN: 33474

American (AMR) AF: 0.550 AC: 24555 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11752 AN: 26132

East Asian (EAS) AF: 0.461 AC: 18283 AN: 39672

South Asian (SAS) AF: 0.679 AC: 58586 AN: 86242

European-Finnish (FIN) AF: 0.638 AC: 33854 AN: 53064

Middle Eastern (MID) AF: 0.510 AC: 2944 AN: 5768

European-Non Finnish (NFE) AF: 0.617 AC: 685509 AN: 1111670

Other (OTH) AF: 0.594 AC: 35850 AN: 60372

GnomAD4 genome AF: 0.589 AC: 89574 AN: 152008 Hom.: 26617 Cov.: 33 AF XY: 0.588 AC XY: 43675 AN XY: 74276

African (AFR) AF: 0.593 AC: 24552 AN: 41408

American (AMR) AF: 0.528 AC: 8081 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1550 AN: 3472

East Asian (EAS) AF: 0.457 AC: 2360 AN: 5166

South Asian (SAS) AF: 0.679 AC: 3270 AN: 4818

European-Finnish (FIN) AF: 0.633 AC: 6699 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41220 AN: 67960

Other (OTH) AF: 0.571 AC: 1204 AN: 2108

Alfa AF: 0.585 Hom.: 44319

Bravo AF: 0.579

Asia WGS AF: 0.615 AC: 2143 AN: 3478

EpiCase AF: 0.587

EpiControl AF: 0.582

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Neuropathy, congenital hypomyelinating, 3 (2)
-	-	1	Lethal congenital contracture syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.51
PhyloP100		2.0
PromoterAI		-0.0065	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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