Variant chr12-40939357-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_001843.4(CNTN1):c.1251G>T(p.Met417Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000364 in 1,613,812 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

CNTN1
NM_001843.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.23

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0060263574).

BP6

Variant 12-40939357-G-T is Benign according to our data. Variant chr12-40939357-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 384608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00196 (299/152214) while in subpopulation AFR AF= 0.0071 (295/41548). AF 95% confidence interval is 0.00643. There are 0 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN1	NM_001843.4 linkuse as main transcript	c.1251G>T	p.Met417Ile	missense_variant	12/24	ENST00000551295.7	NP_001834.2	Q12860-1A0A024R104

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN1	ENST00000551295.7 linkuse as main transcript	c.1251G>T	p.Met417Ile	missense_variant	12/24	1	NM_001843.4	ENSP00000447006.1		Q12860-1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

299

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00712

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000494

AC:

124

AN:

250916

Hom.:

AF XY:

0.000376

AC XY:

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.00689

Gnomad AMR exome

AF:

0.000348

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

289

AN:

1461598

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.00711

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152214

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.00710

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000380

Hom.:

Bravo

AF:

0.00228

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000634

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2022

See Variant Classification Assertion Criteria. -

Compton-North congenital myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Uncertain

0.43

.;T;.;T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.91

.;.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.0060

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;N;N;N;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.2

N;N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.37

T;T;T;T;T

Sift4G

Benign

0.38

T;T;T;T;T

Polyphen

0.061

B;B;B;B;B

Vest4

0.26

MutPred

0.38

Loss of disorder (P = 0.0945);Loss of disorder (P = 0.0945);Loss of disorder (P = 0.0945);Loss of disorder (P = 0.0945);.;

MVP

0.27

MPC

0.39

ClinPred

0.023

GERP RS

4.0

Varity_R

0.16

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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