12-40908032-T-G

Variant names:

• chr12-40908032-T-G
• rs12821990
• NM_001843.4:c.-76-325T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001843.4(CNTN1):​c.-76-325T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0334 in 152,314 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.033 (112 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.655
• Publications: 2 publications found

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]

CNTN1 Gene-Disease associations (from GenCC):

• Compton-North congenital myopathy

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-40908032-T-G is Benign according to our data. Variant chr12-40908032-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 671822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0334 (5092/152314) while in subpopulation SAS AF = 0.0522 (252/4828). AF 95% confidence interval is 0.0469. There are 112 homozygotes in GnomAd4. There are 2498 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 112 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-76-325T>G		intron_variant	Intron 1 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.-76-325T>G		intron_variant	Intron 1 of 23	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes AF: 0.0334 AC: 5084 AN: 152196 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.00861

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0462

Gnomad ASJ AF: 0.0502

Gnomad EAS AF: 0.00634

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0210

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0406

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

GnomAD4 genome AF: 0.0334 AC: 5092 AN: 152314 Hom.: 112 Cov.: 32 AF XY: 0.0335 AC XY: 2498 AN XY: 74474

African (AFR) AF: 0.00864 AC: 359 AN: 41574

American (AMR) AF: 0.0462 AC: 707 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0502 AC: 174 AN: 3468

East Asian (EAS) AF: 0.00635 AC: 33 AN: 5194

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4828

European-Finnish (FIN) AF: 0.0210 AC: 223 AN: 10616

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3147 AN: 68010

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0442 Hom.: 206

Bravo AF: 0.0341

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.1
DANN	Benign	0.77
PhyloP100		0.66
PromoterAI		-0.00090	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12821990; hg19: chr12-41301834;