chr12-40986686-A-C

Position:

• chr12-40986686-A-C

Variant summary

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

The NM_001843.4(CNTN1):​c.1963+5619A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 151,886 control chromosomes in the GnomAD database, including 27,868 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 0.60 (27868 hom., cov: 31)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.1963+5619A>C		intron_variant		ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.1963+5619A>C		intron_variant		1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000347616.5	c.1963+5619A>C		intron_variant		1		ENSP00000325660.3
CNTN1	ENST00000348761.2	c.1930+5619A>C		intron_variant		1		ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91671 AN: 151772 Hom.: 27867 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.604 AC: 91692 AN: 151886 Hom.: 27868 Cov.: 31 AF XY: 0.605 AC XY: 44899 AN XY: 74228

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.444

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.610

Gnomad4 OTH AF: 0.582

Alfa AF: 0.586 Hom.: 10777

Bravo AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.71

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: rs278917; hg19: chr12-41380488;