12-40692833-A-G

Variant names:

• chr12-40692833-A-G
• rs1992607
• NM_001843.4:c.-77+241A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001843.4(CNTN1):​c.-77+241A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,146 control chromosomes in the GnomAD database, including 60,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60245 hom., cov: 32)
• Consequence: CNTN1 NM_001843.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• 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), 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=-0.78).
• BP6: Variant 12-40692833-A-G is Benign according to our data. Variant chr12-40692833-A-G is described in ClinVar as [Benign]. Clinvar id is 1273799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN1	NM_001843.4	c.-77+241A>G		intron_variant	Intron 1 of 23	ENST00000551295.7	NP_001834.2
CNTN1	NM_001256063.2	c.-77+241A>G		intron_variant	Intron 1 of 15		NP_001242992.1
CNTN1	XM_011537926.4	c.-180+241A>G		intron_variant	Intron 1 of 24		XP_011536228.1
CNTN1	XM_024448843.2	c.-180+241A>G		intron_variant	Intron 1 of 16		XP_024304611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7	c.-77+241A>G		intron_variant	Intron 1 of 23	1	NM_001843.4	ENSP00000447006.1
CNTN1	ENST00000547702.5	c.-77+241A>G		intron_variant	Intron 1 of 15	2		ENSP00000448004.1
CNTN1	ENST00000551424.5	c.-237+241A>G		intron_variant	Intron 1 of 4	3		ENSP00000450412.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135148 AN: 152028 Hom.: 60192 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.949

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.888

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.889 AC: 135260 AN: 152146 Hom.: 60245 Cov.: 32 AF XY: 0.892 AC XY: 66352 AN XY: 74380

African (AFR) AF: 0.845 AC: 35074 AN: 41516

American (AMR) AF: 0.935 AC: 14294 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2913 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5112 AN: 5120

South Asian (SAS) AF: 0.949 AC: 4576 AN: 4822

European-Finnish (FIN) AF: 0.901 AC: 9551 AN: 10606

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60718 AN: 67994

Other (OTH) AF: 0.890 AC: 1883 AN: 2116

Alfa AF: 0.885 Hom.: 8700

Bravo AF: 0.888

Asia WGS AF: 0.967 AC: 3362 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 03, 2018

GeneDx

Significance: 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	-0.78
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		1.6
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs1992607; hg19: chr12-41086635;