rs10784981

chr12-40980895-C-Achr12-40980895-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001843.4(CNTN1):c.1805-14C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,611,240 control chromosomes in the GnomAD database, including 11,974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1087 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10887 hom.)
• Consequence: CNTN1 NM_001843.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.289

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=-0.78).
• BP6: Variant 12-40980895-C-A is Benign according to our data. Variant chr12-40980895-C-A is described in ClinVar as [Benign]. Clinvar id is 258193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-40980895-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.1805-14C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.1805-14C>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001843.4	P3
CNTN1	ENST00000347616.5	c.1805-14C>A		splice_polypyrimidine_tract_variant, intron_variant		1		P3
CNTN1	ENST00000348761.2	c.1772-14C>A		splice_polypyrimidine_tract_variant, intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17833 AN: 152078 Hom.: 1087 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.112

GnomAD3 exomes AF: 0.111 AC: 27869 AN: 250562 Hom.: 1682 AF XY: 0.111 AC XY: 15056 AN XY: 135430

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.0651

Gnomad SAS exome AF: 0.0746

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.121

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.119 AC: 174091 AN: 1459044 Hom.: 10887 Cov.: 31 AF XY: 0.118 AC XY: 85710 AN XY: 726006

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.0517

Gnomad4 SAS exome AF: 0.0766

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.117 AC: 17839 AN: 152196 Hom.: 1087 Cov.: 32 AF XY: 0.117 AC XY: 8687 AN XY: 74422

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0672 Hom.: 114

Bravo AF: 0.116

Asia WGS AF: 0.0780 AC: 270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 08, 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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	3.7
Dann	Benign	0.59

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: rs10784981; hg19: chr12-41374697;