12-40808995-G-C

Position:

• chr12-40808995-G-C

Variant summary

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

The NM_001843.4(CNTN1):​c.-76-99362G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 151,828 control chromosomes in the GnomAD database, including 24,347 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 0.56 (24347 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-76-99362G>C		intron_variant		ENST00000551295.7	NP_001834.2
CNTN1	NM_001256063.2	c.-76-99362G>C		intron_variant			NP_001242992.1
CNTN1	XM_011537926.4	c.-77+45797G>C		intron_variant			XP_011536228.1
CNTN1	XM_024448843.2	c.-77+45797G>C		intron_variant			XP_024304611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.-76-99362G>C		intron_variant		1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85179 AN: 151710 Hom.: 24311 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.534

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.559

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

GnomAD4 genome AF: 0.562 AC: 85253 AN: 151828 Hom.: 24347 Cov.: 32 AF XY: 0.565 AC XY: 41952 AN XY: 74208

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.564

Alfa AF: 0.549 Hom.: 2788

Bravo AF: 0.566

Asia WGS AF: 0.650 AC: 2257 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.73

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: rs984129; hg19: chr12-41202797;