12-41020410-T-C

Variant names:

• chr12-41020410-T-C
• rs61754102
• NM_001843.4:c.2493T>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.2493T>C​(p.His831His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,611,820 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (80 hom.)
• Consequence: CNTN1 NM_001843.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0150
• Publications: 2 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=-0.52).
• BP6: Variant 12-41020410-T-C is Benign according to our data. Variant chr12-41020410-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.015 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00443 (675/152296) while in subpopulation SAS AF = 0.0159 (77/4830). AF 95% confidence interval is 0.0131. There are 7 homozygotes in GnomAd4. There are 360 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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.2493T>C	p.His831His	synonymous	Exon 20 of 24	NP_001834.2
	CNTN1	NM_175038.2		c.2460T>C	p.His820His	synonymous	Exon 18 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.2493T>C	p.His831His	synonymous	Exon 20 of 24	ENSP00000447006.1	Q12860-1
	CNTN1	ENST00000347616.5	TSL:1	c.2493T>C	p.His831His	synonymous	Exon 19 of 23	ENSP00000325660.3	Q12860-1
	CNTN1	ENST00000348761.2	TSL:1	c.2460T>C	p.His820His	synonymous	Exon 18 of 22	ENSP00000261160.3	Q12860-2

Frequencies

GnomAD3 genomes AF: 0.00444 AC: 676 AN: 152178 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00440

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.00714 AC: 1789 AN: 250498 AF XY: 0.00823

Gnomad AFR exome AF: 0.000557

Gnomad AMR exome AF: 0.00438

Gnomad ASJ exome AF: 0.0398

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000462

Gnomad NFE exome AF: 0.00512

Gnomad OTH exome AF: 0.00918

GnomAD4 exome AF: 0.00488 AC: 7127 AN: 1459524 Hom.: 80 Cov.: 29 AF XY: 0.00556 AC XY: 4040 AN XY: 726120

African (AFR) AF: 0.000479 AC: 16 AN: 33426

American (AMR) AF: 0.00436 AC: 195 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0379 AC: 988 AN: 26080

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39534

South Asian (SAS) AF: 0.0193 AC: 1658 AN: 85920

European-Finnish (FIN) AF: 0.000525 AC: 28 AN: 53376

Middle Eastern (MID) AF: 0.0338 AC: 194 AN: 5732

European-Non Finnish (NFE) AF: 0.00320 AC: 3557 AN: 1110502

Other (OTH) AF: 0.00813 AC: 490 AN: 60276

GnomAD4 genome AF: 0.00443 AC: 675 AN: 152296 Hom.: 7 Cov.: 33 AF XY: 0.00484 AC XY: 360 AN XY: 74456

African (AFR) AF: 0.000625 AC: 26 AN: 41584

American (AMR) AF: 0.00556 AC: 85 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3468

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4830

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00440 AC: 299 AN: 67996

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.00675 Hom.: 4

Bravo AF: 0.00433

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.52
CADD	Benign	4.3
DANN	Benign	0.56
PhyloP100		-0.015
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: rs61754102; hg19: chr12-41414212;