rs10506176

Positions:

• chr12-40880998-G-T

Variant summary

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

The NM_001843.4(CNTN1):​c.-76-27359G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0491 in 152,008 control chromosomes in the GnomAD database, including 410 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 0.049 (410 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN1	NM_001843.4	c.-76-27359G>T		intron_variant		ENST00000551295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN1	ENST00000551295.7	c.-76-27359G>T		intron_variant		1	NM_001843.4	P3

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7445 AN: 151890 Hom.: 409 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0225

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.00838

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0141

Gnomad OTH AF: 0.0378

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

GnomAD4 genome AF: 0.0491 AC: 7466 AN: 152008 Hom.: 410 Cov.: 32 AF XY: 0.0473 AC XY: 3518 AN XY: 74342

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0225

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.00838

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0374

Alfa AF: 0.0429 Hom.: 59

Bravo AF: 0.0539

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.89
DANN	Benign	0.54

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: rs10506176; hg19: chr12-41274800; COSMIC: COSV73505155;