12-40908567-G-A

Variant names:

• chr12-40908567-G-A
• rs78150049
• NM_001843.4:c.61+74G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001843.4(CNTN1):​c.61+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,117,940 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (20 hom.)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.23
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-40908567-G-A is Benign according to our data. Variant chr12-40908567-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1186439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1954/152238) while in subpopulation AFR AF = 0.0443 (1839/41534). AF 95% confidence interval is 0.0426. There are 42 homozygotes in GnomAd4. There are 892 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.61+74G>A		intron_variant	Intron 2 of 23	ENST00000551295.7	NP_001834.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.61+74G>A		intron_variant	Intron 2 of 23	1	NM_001843.4	ENSP00000447006.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1949 AN: 152120 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00814

GnomAD4 exome AF: 0.00129 AC: 1244 AN: 965702 Hom.: 20 AF XY: 0.00115 AC XY: 568 AN XY: 494882

African (AFR) AF: 0.0439 AC: 979 AN: 22326

American (AMR) AF: 0.00321 AC: 114 AN: 35480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21508

East Asian (EAS) AF: 0.00 AC: 0 AN: 35534

South Asian (SAS) AF: 0.000132 AC: 9 AN: 68430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43518

Middle Eastern (MID) AF: 0.00222 AC: 7 AN: 3154

European-Non Finnish (NFE) AF: 0.0000549 AC: 38 AN: 692462

Other (OTH) AF: 0.00224 AC: 97 AN: 43290

GnomAD4 genome AF: 0.0128 AC: 1954 AN: 152238 Hom.: 42 Cov.: 32 AF XY: 0.0120 AC XY: 892 AN XY: 74434

African (AFR) AF: 0.0443 AC: 1839 AN: 41534

American (AMR) AF: 0.00549 AC: 84 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68010

Other (OTH) AF: 0.00806 AC: 17 AN: 2110

Alfa AF: 0.00175 Hom.: 1

Bravo AF: 0.0140

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 09, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.71
PhyloP100		-1.2
PromoterAI		-0.00040	Neutral
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: rs78150049; hg19: chr12-41302369;