rs2229929

chr12-40980997-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001843.4(CNTN1):c.1893T>C(p.His631=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,613,680 control chromosomes in the GnomAD database, including 580 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (294 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (286 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.119

Genes affected

CNTN1 (HGNC:2171): (contactin 1) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-40980997-T-C is Benign according to our data. Variant chr12-40980997-T-C is described in ClinVar as [Benign]. Clinvar id is 128792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.119 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.1893T>C	p.His631=	synonymous_variant	16/24	ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.1893T>C	p.His631=	synonymous_variant	16/24	1	NM_001843.4	P3
CNTN1	ENST00000347616.5	c.1893T>C	p.His631=	synonymous_variant	15/23	1		P3
CNTN1	ENST00000348761.2	c.1860T>C	p.His620=	synonymous_variant	14/22	1		A1

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5241 AN: 152174 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0249

GnomAD3 exomes AF: 0.0100 AC: 2518 AN: 250908 Hom.: 136 AF XY: 0.00773 AC XY: 1048 AN XY: 135570

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.00550

Gnomad ASJ exome AF: 0.00169

Gnomad EAS exome AF: 0.00316

Gnomad SAS exome AF: 0.00503

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00395 AC: 5777 AN: 1461388 Hom.: 286 Cov.: 31 AF XY: 0.00357 AC XY: 2593 AN XY: 727022

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.00642

Gnomad4 ASJ exome AF: 0.00134

Gnomad4 EAS exome AF: 0.00151

Gnomad4 SAS exome AF: 0.00468

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000255

Gnomad4 OTH exome AF: 0.00779

GnomAD4 genome AF: 0.0346 AC: 5262 AN: 152292 Hom.: 294 Cov.: 32 AF XY: 0.0330 AC XY: 2456 AN XY: 74474

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.0132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0193 Hom.: 94

Bravo AF: 0.0393

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Compton-North congenital myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	3.7
Dann	Benign	0.53

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: rs2229929; hg19: chr12-41374799;