rs61759480

chr12-40943618-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001843.4(CNTN1):c.1401T>C(p.Gly467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,588,330 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (23 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.82

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=-0.79).
• BP6: Variant 12-40943618-T-C is Benign according to our data. Variant chr12-40943618-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00204 (310/152196) while in subpopulation NFE AF= 0.00349 (237/67998). AF 95% confidence interval is 0.00312. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.1401T>C	p.Gly467=	synonymous_variant	13/24	ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.1401T>C	p.Gly467=	synonymous_variant	13/24	1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152078 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00190 AC: 475 AN: 249892 Hom.: 2 AF XY: 0.00194 AC XY: 262 AN XY: 135038

Gnomad AFR exome AF: 0.000987

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00341

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00356 AC: 5111 AN: 1436134 Hom.: 23 Cov.: 27 AF XY: 0.00346 AC XY: 2479 AN XY: 716070

Gnomad4 AFR exome AF: 0.000486

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000116

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00300

Gnomad4 NFE exome AF: 0.00441

Gnomad4 OTH exome AF: 0.00212

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152196 Hom.: 1 Cov.: 32 AF XY: 0.00169 AC XY: 126 AN XY: 74410

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.000394

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00349

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00296 Hom.: 0

Bravo AF: 0.00198

EpiCase AF: 0.00219

EpiControl AF: 0.00267

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 22, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	CNTN1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 06, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Compton-North congenital myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	4.2
Dann	Benign	0.63

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: rs61759480; hg19: chr12-41337420;