Variant chr12-40908421-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001843.4(CNTN1):c.-12A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,612,220 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0078 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 10 hom. )

Consequence

CNTN1
NM_001843.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.130

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-40908421-A-G is Benign according to our data. Variant chr12-40908421-A-G is described in ClinVar as [Benign]. Clinvar id is 384607.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00784 (1194/152222) while in subpopulation AFR AF= 0.0274 (1137/41540). AF 95% confidence interval is 0.026. There are 17 homozygotes in gnomad4. There are 553 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4 linkuse as main transcript	c.-12A>G		5_prime_UTR_premature_start_codon_gain_variant	2/24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104
CNTN1	NM_001843.4 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	2/24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295 linkuse as main transcript	c.-12A>G		5_prime_UTR_premature_start_codon_gain_variant	2/24	1	NM_001843.4	ENSP00000447006.1		Q12860-1
CNTN1	ENST00000551295 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	2/24	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

AF:

0.00784

AC:

1193

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00196

AC:

491

AN:

250782

Hom.:

AF XY:

0.00141

AC XY:

191

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000776

AC:

1133

AN:

1459998

Hom.:

Cov.:

AF XY:

0.000657

AC XY:

477

AN XY:

726412

show subpopulations

Gnomad4 AFR exome

AF:

0.0277

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000486

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.00784

AC:

1194

AN:

152222

Hom.:

Cov.:

AF XY:

0.00743

AC XY:

553

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0274

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00875

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

DANN

Benign

0.27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over