12-40908306-C-G

Variant names:

• chr12-40908306-C-G
• rs80139511
• NM_001843.4:c.-76-51C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001843.4(CNTN1):​c.-76-51C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0675 in 647,696 control chromosomes in the GnomAD database, including 2,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (549 hom., cov: 32)
  • Exomes 𝑓: 0.068 (2124 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.890
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-40908306-C-G is Benign according to our data. Variant chr12-40908306-C-G is described in ClinVar as Benign. ClinVar VariationId is 1293333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	NM_001843.4	MANE Select	c.-76-51C>G		intron	N/A	NP_001834.2
	CNTN1	NM_001256063.2		c.-76-51C>G		intron	N/A	NP_001242992.1	Q12860-3
	CNTN1	NM_001256064.2		c.-76-51C>G		intron	N/A	NP_001242993.1	Q12860-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.-76-51C>G		intron	N/A	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000547849.6	TSL:1	c.-76-51C>G		intron	N/A	ENSP00000448653.1	Q12860-3
	CNTN1	ENST00000901030.1		c.-76-51C>G		intron	N/A	ENSP00000571089.1

Frequencies

GnomAD3 genomes AF: 0.0666 AC: 10111 AN: 151902 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0365

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0647

GnomAD4 exome AF: 0.0677 AC: 33576 AN: 495676 Hom.: 2124 Cov.: 7 AF XY: 0.0645 AC XY: 17134 AN XY: 265778

African (AFR) AF: 0.0439 AC: 560 AN: 12746

American (AMR) AF: 0.246 AC: 5170 AN: 21000

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 1009 AN: 16110

East Asian (EAS) AF: 0.167 AC: 5005 AN: 29958

South Asian (SAS) AF: 0.0342 AC: 1592 AN: 46588

European-Finnish (FIN) AF: 0.132 AC: 4929 AN: 37378

Middle Eastern (MID) AF: 0.0793 AC: 260 AN: 3280

European-Non Finnish (NFE) AF: 0.0444 AC: 13383 AN: 301418

Other (OTH) AF: 0.0613 AC: 1668 AN: 27198

GnomAD4 genome AF: 0.0666 AC: 10120 AN: 152020 Hom.: 549 Cov.: 32 AF XY: 0.0728 AC XY: 5410 AN XY: 74282

African (AFR) AF: 0.0412 AC: 1709 AN: 41518

American (AMR) AF: 0.166 AC: 2529 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 222 AN: 3468

East Asian (EAS) AF: 0.147 AC: 757 AN: 5156

South Asian (SAS) AF: 0.0364 AC: 175 AN: 4812

European-Finnish (FIN) AF: 0.145 AC: 1527 AN: 10538

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3003 AN: 67942

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0299 Hom.: 20

Bravo AF: 0.0726

Asia WGS AF: 0.0790 AC: 273 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.89
PromoterAI		-0.0022	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: rs80139511; hg19: chr12-41302108; COSMIC: COSV61640573; COSMIC: COSV61640573;