rs61748365

Variant names:

• chr12-40910101-T-C
• rs61748365
• NM_001843.4:c.90T>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 NM_001843.4(CNTN1):​c.90T>C​(p.His30His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,605,248 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0068 (14 hom., cov: 32)
  • Exomes 𝑓: 0.012 (135 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.00
• Publications: 4 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=-0.5).
• BP6: Variant 12-40910101-T-C is Benign according to our data. Variant chr12-40910101-T-C is described in ClinVar as Benign. ClinVar VariationId is 258204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.01 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0068 (1035/152302) while in subpopulation NFE AF = 0.0125 (849/68006). AF 95% confidence interval is 0.0118. There are 14 homozygotes in GnomAd4. There are 472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 14 AR,Unknown gene

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.90T>C	p.His30His	synonymous	Exon 3 of 24	NP_001834.2
	CNTN1	NM_001256063.2		c.90T>C	p.His30His	synonymous	Exon 3 of 16	NP_001242992.1	Q12860-3
	CNTN1	NM_001256064.2		c.90T>C	p.His30His	synonymous	Exon 3 of 16	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.90T>C	p.His30His	synonymous	Exon 3 of 24	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.90T>C	p.His30His	synonymous	Exon 2 of 23	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000547849.6	TSL:1	c.90T>C	p.His30His	synonymous	Exon 3 of 16	ENSP00000448653.1	Q12860-3

Frequencies

GnomAD3 genomes AF: 0.00680 AC: 1035 AN: 152184 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00624 AC: 1565 AN: 250910 AF XY: 0.00657

Gnomad AFR exome AF: 0.00252

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00107

Gnomad NFE exome AF: 0.0116

Gnomad OTH exome AF: 0.00539

GnomAD4 exome AF: 0.0115 AC: 16741 AN: 1452946 Hom.: 135 Cov.: 27 AF XY: 0.0112 AC XY: 8127 AN XY: 723418

African (AFR) AF: 0.00183 AC: 61 AN: 33332

American (AMR) AF: 0.00320 AC: 143 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26010

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

South Asian (SAS) AF: 0.00163 AC: 140 AN: 85992

European-Finnish (FIN) AF: 0.00132 AC: 70 AN: 52868

Middle Eastern (MID) AF: 0.00210 AC: 12 AN: 5722

European-Non Finnish (NFE) AF: 0.0142 AC: 15681 AN: 1104770

Other (OTH) AF: 0.00963 AC: 579 AN: 60094

GnomAD4 genome AF: 0.00680 AC: 1035 AN: 152302 Hom.: 14 Cov.: 32 AF XY: 0.00634 AC XY: 472 AN XY: 74478

African (AFR) AF: 0.00274 AC: 114 AN: 41576

American (AMR) AF: 0.00294 AC: 45 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0125 AC: 849 AN: 68006

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00916 Hom.: 3

Bravo AF: 0.00746

Asia WGS AF: 0.00116 AC: 4 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Compton-North congenital myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.9
DANN	Benign	0.58
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61748365; hg19: chr12-41303903;