rs181426756

Positions:

• chr12-41029238-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001843.4(CNTN1):​c.2980+19A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00215 in 1,613,786 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (18 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.0910

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-41029238-A-T is Benign according to our data. Variant chr12-41029238-A-T is described in ClinVar as [Benign]. Clinvar id is 258199.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00157 (239/152264) while in subpopulation SAS AF= 0.0126 (61/4824). AF 95% confidence interval is 0.0101. There are 2 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.2980+19A>T		intron_variant		ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.2980+19A>T		intron_variant		1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.2980+19A>T		intron_variant		1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.2947+19A>T		intron_variant		1		ENSP00000261160.3
CNTN1	ENST00000548481.1	n.106+19A>T		intron_variant		3		ENSP00000449517.1

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 240 AN: 152146 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00294 AC: 738 AN: 250916 Hom.: 6 AF XY: 0.00350 AC XY: 474 AN XY: 135600

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00487

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0119

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00221 AC: 3228 AN: 1461522 Hom.: 18 Cov.: 30 AF XY: 0.00261 AC XY: 1900 AN XY: 727100

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.00199

Gnomad4 ASJ exome AF: 0.00356

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00318

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152264 Hom.: 2 Cov.: 32 AF XY: 0.00172 AC XY: 128 AN XY: 74450

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00219 Hom.: 0

Bravo AF: 0.00151

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2017	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:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Feb 16, 2022	- -

not provided Benign:1

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	-0.82
CADD	Benign	6.7
DANN	Benign	0.60

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: rs181426756; hg19: chr12-41423040;