12-40959947-C-T

Position:

• chr12-40959947-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001843.4(CNTN1):​c.1804+713C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,014 control chromosomes in the GnomAD database, including 961 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (961 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.1804+713C>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.1804+713C>T		intron_variant		1	NM_001843.4	ENSP00000447006	P3

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 14986 AN: 151896 Hom.: 959 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0351

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0987 AC: 14997 AN: 152014 Hom.: 961 Cov.: 32 AF XY: 0.0958 AC XY: 7117 AN XY: 74298

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0593

Gnomad4 ASJ AF: 0.0415

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0658

Gnomad4 NFE AF: 0.0769

Gnomad4 OTH AF: 0.0779

Alfa AF: 0.0741 Hom.: 941

Bravo AF: 0.0992

Asia WGS AF: 0.0430 AC: 150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.3
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: rs13328933; hg19: chr12-41353749;