rs61759480

Variant names:

• chr12-40943618-T-C
• rs61759480
• NM_001843.4:c.1401T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000551295.7(CNTN1):​c.1401T>C​(p.Gly467Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00341 in 1,588,330 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (23 hom.)
• Consequence: CNTN1 ENST00000551295.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.82
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 12-40943618-T-C is Benign according to our data. Variant chr12-40943618-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00204 (310/152196) while in subpopulation NFE AF = 0.00349 (237/67998). AF 95% confidence interval is 0.00312. There are 1 homozygotes in GnomAd4. There are 126 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 23 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551295.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	NM_001843.4	MANE Select	c.1401T>C	p.Gly467Gly	synonymous	Exon 13 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.1368T>C	p.Gly456Gly	synonymous	Exon 11 of 22	NP_778203.1
	CNTN1	NM_001256063.2		c.1401T>C	p.Gly467Gly	synonymous	Exon 13 of 16	NP_001242992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN1	ENST00000551295.7	TSL:1 MANE Select	c.1401T>C	p.Gly467Gly	synonymous	Exon 13 of 24	ENSP00000447006.1
	CNTN1	ENST00000347616.5	TSL:1	c.1401T>C	p.Gly467Gly	synonymous	Exon 12 of 23	ENSP00000325660.3
	CNTN1	ENST00000348761.2	TSL:1	c.1368T>C	p.Gly456Gly	synonymous	Exon 11 of 22	ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152078 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00190 AC: 475 AN: 249892 AF XY: 0.00194

Gnomad AFR exome AF: 0.000987

Gnomad AMR exome AF: 0.000232

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00245

Gnomad NFE exome AF: 0.00341

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00356 AC: 5111 AN: 1436134 Hom.: 23 Cov.: 27 AF XY: 0.00346 AC XY: 2479 AN XY: 716070

African (AFR) AF: 0.000486 AC: 16 AN: 32926

American (AMR) AF: 0.000179 AC: 8 AN: 44620

Ashkenazi Jewish (ASJ) AF: 0.000116 AC: 3 AN: 25924

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85796

European-Finnish (FIN) AF: 0.00300 AC: 160 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00441 AC: 4796 AN: 1088758

Other (OTH) AF: 0.00212 AC: 126 AN: 59560

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152196 Hom.: 1 Cov.: 32 AF XY: 0.00169 AC XY: 126 AN XY: 74410

African (AFR) AF: 0.000866 AC: 36 AN: 41554

American (AMR) AF: 0.000394 AC: 6 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00349 AC: 237 AN: 67998

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00296 Hom.: 0

Bravo AF: 0.00198

EpiCase AF: 0.00219

EpiControl AF: 0.00267

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Compton-North congenital myopathy (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs61759480; hg19: chr12-41337420;