Variant 3-74266626-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The ENST00000263665.7(CNTN3):c.2841A>G(p.Gln947=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,613,350 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 26 hom. )

Consequence

CNTN3
ENST00000263665.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.626

Variant links:

Genes affected

CNTN3 (HGNC:2173): (contactin 3) Predicted to be involved in cell adhesion and nervous system development. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in neuron projection. [provided by Alliance of Genome Resources, Apr 2022]

CNTN3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-74266626-T-C is Benign according to our data. Variant chr3-74266626-T-C is described in ClinVar as [Benign]. Clinvar id is 716102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.626 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1639/152284) while in subpopulation AFR AF= 0.0379 (1576/41548). AF 95% confidence interval is 0.0364. There are 34 homozygotes in gnomad4. There are 771 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNTN3	NM_020872.3 linkuse as main transcript	c.2841A>G	p.Gln947=	synonymous_variant	22/23	ENST00000263665.7	NP_065923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN3	ENST00000263665.7 linkuse as main transcript	c.2841A>G	p.Gln947=	synonymous_variant	22/23	1	NM_020872.3	ENSP00000263665	P1
CNTN3	ENST00000477856.1 linkuse as main transcript	n.298A>G		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1633

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0379

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00275

AC:

690

AN:

250906

Hom.:

AF XY:

0.00194

AC XY:

263

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.0374

Gnomad AMR exome

AF:

0.00171

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:

0.000123

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00106

AC:

1553

AN:

1461066

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

691

AN XY:

726824

show subpopulations

Gnomad4 AFR exome

AF:

0.0374

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.0108

AC:

1639

AN:

152284

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

771

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00452

Hom.:

Bravo

AF:

0.0114

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.8

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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