12-40692480-C-A

Variant names:

• chr12-40692480-C-A
• rs11177830
• NM_001843.4:c.-189C>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The NM_001843.4(CNTN1):​c.-189C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 152,564 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.063 (347 hom., cov: 32)
  • Exomes 𝑓: 0.071 (1 hom.)
• Consequence: CNTN1 NM_001843.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.80
• Publications: 11 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BP6: Variant 12-40692480-C-A is Benign according to our data. Variant chr12-40692480-C-A is described in ClinVar as [Benign]. Clinvar id is 1271001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-189C>A		5_prime_UTR_variant	Exon 1 of 24	ENST00000551295.7	NP_001834.2
CNTN1	NM_001256063.2	c.-189C>A		5_prime_UTR_variant	Exon 1 of 16		NP_001242992.1
CNTN1	XM_011537926.4	c.-292C>A		5_prime_UTR_variant	Exon 1 of 25		XP_011536228.1
CNTN1	XM_024448843.2	c.-292C>A		5_prime_UTR_variant	Exon 1 of 17		XP_024304611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.-189C>A		5_prime_UTR_variant	Exon 1 of 24	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000547702.5	c.-189C>A		5_prime_UTR_variant	Exon 1 of 16	2		ENSP00000448004.1
CNTN1	ENST00000551424.5	c.-349C>A		5_prime_UTR_variant	Exon 1 of 5	3		ENSP00000450412.1

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9577 AN: 152068 Hom.: 345 Cov.: 32

Gnomad AFR AF: 0.0458

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0297

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0508

GnomAD4 exome AF: 0.0714 AC: 27 AN: 378 Hom.: 1 Cov.: 0 AF XY: 0.0714 AC XY: 21 AN XY: 294

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AF: 0.00 AC: 0 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 20

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0786 AC: 25 AN: 318

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.0630 AC: 9584 AN: 152186 Hom.: 347 Cov.: 32 AF XY: 0.0618 AC XY: 4600 AN XY: 74402

African (AFR) AF: 0.0458 AC: 1903 AN: 41532

American (AMR) AF: 0.0500 AC: 764 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0303 AC: 146 AN: 4816

European-Finnish (FIN) AF: 0.0943 AC: 998 AN: 10578

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5416 AN: 68004

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

Alfa AF: 0.0211 Hom.: 9

Bravo AF: 0.0590

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		1.8
PromoterAI		0.027	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11177830; hg19: chr12-41086282;