rs2229930

Variant names:

• chr12-40981060-A-G
• rs2229930
• NM_001843.4:c.1956A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001843.4(CNTN1):​c.1956A>G​(p.Ala652Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0414 in 1,612,264 control chromosomes in the GnomAD database, including 1,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (110 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1501 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.71
• Publications: 6 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), Orphanet, Ambry Genetics
• schizophrenia

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 12-40981060-A-G is Benign according to our data. Variant chr12-40981060-A-G is described in ClinVar as Benign. ClinVar VariationId is 128793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.71 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0508 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.1956A>G	p.Ala652Ala	synonymous	Exon 16 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.1923A>G	p.Ala641Ala	synonymous	Exon 14 of 22	NP_778203.1	Q12860-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.1956A>G	p.Ala652Ala	synonymous	Exon 16 of 24	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.1956A>G	p.Ala652Ala	synonymous	Exon 15 of 23	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.1923A>G	p.Ala641Ala	synonymous	Exon 14 of 22	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 5055 AN: 152244 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.00846

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00653

Gnomad SAS AF: 0.0554

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0399 AC: 10004 AN: 250718 AF XY: 0.0415

Gnomad AFR exome AF: 0.00806

Gnomad AMR exome AF: 0.0463

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.00500

Gnomad FIN exome AF: 0.0214

Gnomad NFE exome AF: 0.0458

Gnomad OTH exome AF: 0.0507

GnomAD4 exome AF: 0.0422 AC: 61649 AN: 1459902 Hom.: 1501 Cov.: 31 AF XY: 0.0429 AC XY: 31146 AN XY: 726274

African (AFR) AF: 0.00814 AC: 272 AN: 33430

American (AMR) AF: 0.0485 AC: 2167 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 1308 AN: 26114

East Asian (EAS) AF: 0.00542 AC: 215 AN: 39672

South Asian (SAS) AF: 0.0561 AC: 4837 AN: 86196

European-Finnish (FIN) AF: 0.0208 AC: 1110 AN: 53402

Middle Eastern (MID) AF: 0.0922 AC: 444 AN: 4814

European-Non Finnish (NFE) AF: 0.0440 AC: 48890 AN: 1111336

Other (OTH) AF: 0.0399 AC: 2406 AN: 60248

GnomAD4 genome AF: 0.0332 AC: 5059 AN: 152362 Hom.: 110 Cov.: 32 AF XY: 0.0331 AC XY: 2469 AN XY: 74500

African (AFR) AF: 0.00849 AC: 353 AN: 41592

American (AMR) AF: 0.0467 AC: 715 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3472

East Asian (EAS) AF: 0.00655 AC: 34 AN: 5194

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4834

European-Finnish (FIN) AF: 0.0203 AC: 216 AN: 10626

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0458 AC: 3116 AN: 68026

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0418 Hom.: 132

Bravo AF: 0.0340

Asia WGS AF: 0.0290 AC: 102 AN: 3476

EpiCase AF: 0.0457

EpiControl AF: 0.0484

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	Compton-North congenital myopathy (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.45
DANN	Benign	0.56
PhyloP100		-1.7
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: rs2229930; hg19: chr12-41374862;