Variant 3-1227923-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001289080.2(CNTN6):c.288C>T(p.Gly96=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0093 in 1,613,952 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 102 hom. )

Consequence

CNTN6
NM_001289080.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.764

Variant links:

Genes affected

CNTN6 (HGNC:2176): (contactin 6) 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CNTN6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-1227923-C-T is Benign according to our data. Variant chr3-1227923-C-T is described in ClinVar as [Benign]. Clinvar id is 773864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00599 (912/152208) while in subpopulation SAS AF= 0.0186 (90/4826). AF 95% confidence interval is 0.0155. There are 10 homozygotes in gnomad4. There are 400 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN6	NM_001289080.2 linkuse as main transcript	c.288C>T	p.Gly96=	synonymous_variant	4/23	ENST00000446702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CNTN6	ENST00000446702.7 linkuse as main transcript	c.288C>T	p.Gly96=	synonymous_variant	4/23	1	NM_001289080.2	P1
CNTN6	ENST00000350110.2 linkuse as main transcript	c.288C>T	p.Gly96=	synonymous_variant	4/23	1		P1
CNTN6	ENST00000394261.2 linkuse as main transcript	c.*266C>T		3_prime_UTR_variant, NMD_transcript_variant	5/8	1
CNTN6	ENST00000397479.6 linkuse as main transcript	c.*426C>T		3_prime_UTR_variant, NMD_transcript_variant	3/22	2

Frequencies

GnomAD3 genomes

AF:

0.00600

AC:

912

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.00321

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00970

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00756

AC:

1899

AN:

251276

Hom.:

AF XY:

0.00852

AC XY:

1157

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.00397

Gnomad NFE exome

AF:

0.00920

Gnomad OTH exome

AF:

0.00881

GnomAD4 exome

AF:

0.00964

AC:

14092

AN:

1461744

Hom.:

102

Cov.:

AF XY:

0.00984

AC XY:

7155

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.00559

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0172

Gnomad4 FIN exome

AF:

0.00470

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.00841

GnomAD4 genome

AF:

0.00599

AC:

912

AN:

152208

Hom.:

Cov.:

AF XY:

0.00538

AC XY:

400

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0186

Gnomad4 FIN

AF:

0.00321

Gnomad4 NFE

AF:

0.00970

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00863

Hom.:

Bravo

AF:

0.00543

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.00788

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CNTN6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

Cadd

Benign

Dann

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.44

Position offset: -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