rs7297132

Variant names:

• chr12-40918751-C-T
• rs7297132
• NM_001843.4:c.207C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The ENST00000551295.7(CNTN1):​c.207C>T​(p.Ala69Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,613,610 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0082 (51 hom.)
• Consequence: CNTN1 ENST00000551295.7 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.792
• 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), Ambry Genetics, Orphanet
• schizophrenia

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

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-40918751-C-T is Benign according to our data. Variant chr12-40918751-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00575 (875/152252) while in subpopulation AMR AF = 0.00877 (134/15282). AF 95% confidence interval is 0.00794. There are 4 homozygotes in GnomAd4. There are 400 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 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.207C>T	p.Ala69Ala	synonymous	Exon 4 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.174C>T	p.Ala58Ala	synonymous	Exon 2 of 22	NP_778203.1
	CNTN1	NM_001256063.2		c.207C>T	p.Ala69Ala	synonymous	Exon 4 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.207C>T	p.Ala69Ala	synonymous	Exon 4 of 24	ENSP00000447006.1
	CNTN1	ENST00000347616.5	TSL:1	c.207C>T	p.Ala69Ala	synonymous	Exon 3 of 23	ENSP00000325660.3
	CNTN1	ENST00000348761.2	TSL:1	c.174C>T	p.Ala58Ala	synonymous	Exon 2 of 22	ENSP00000261160.3

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152134 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00171

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.00878

Gnomad ASJ AF: 0.00865

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00570 AC: 1431 AN: 251166 AF XY: 0.00569

Gnomad AFR exome AF: 0.00148

Gnomad AMR exome AF: 0.00613

Gnomad ASJ exome AF: 0.00754

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000970

Gnomad NFE exome AF: 0.00908

Gnomad OTH exome AF: 0.00621

GnomAD4 exome AF: 0.00819 AC: 11963 AN: 1461358 Hom.: 51 Cov.: 32 AF XY: 0.00789 AC XY: 5738 AN XY: 726986

African (AFR) AF: 0.00140 AC: 47 AN: 33460

American (AMR) AF: 0.00653 AC: 292 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00812 AC: 212 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.000788 AC: 68 AN: 86250

European-Finnish (FIN) AF: 0.00118 AC: 63 AN: 53412

Middle Eastern (MID) AF: 0.00399 AC: 23 AN: 5768

European-Non Finnish (NFE) AF: 0.00973 AC: 10820 AN: 1111578

Other (OTH) AF: 0.00725 AC: 438 AN: 60376

GnomAD4 genome AF: 0.00575 AC: 875 AN: 152252 Hom.: 4 Cov.: 32 AF XY: 0.00537 AC XY: 400 AN XY: 74428

African (AFR) AF: 0.00171 AC: 71 AN: 41566

American (AMR) AF: 0.00877 AC: 134 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 30 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4814

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00851 AC: 579 AN: 68014

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00766 Hom.: 2

Bravo AF: 0.00706

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00714

EpiControl AF: 0.00919

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.24		Position offset: 20

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

Other links and lift over

dbSNP: rs7297132; hg19: chr12-41312553; COSMIC: COSV61643280; COSMIC: COSV61643280;