11-100061278-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014361.4(CNTN5):c.1047A>T(p.Lys349Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,613,660 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 14 hom. )

Consequence

CNTN5
NM_014361.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.661

Publications

3 publications found

Variant links:

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein 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. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

CNTN5 links:

LOC105369456 (HGNC:):

LOC105369456 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009718627).

BP6

Variant 11-100061278-A-T is Benign according to our data. Variant chr11-100061278-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00104 (1523/1461362) while in subpopulation AMR AF = 0.0178 (798/44716). AF 95% confidence interval is 0.0168. There are 14 homozygotes in GnomAdExome4. There are 698 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4 link	c.1047A>T	p.Lys349Asn	missense_variant	Exon 10 of 25	ENST00000524871.6	NP_055176.1	O94779-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6 link	c.1047A>T	p.Lys349Asn	missense_variant	Exon 10 of 25	1	NM_014361.4	ENSP00000435637.1		O94779-1

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

229

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0129

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00393

AC:

978

AN:

248988

AF XY:

0.00319

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.00232

GnomAD4 exome

AF:

0.00104

AC:

1523

AN:

1461362

Hom.:

Cov.:

AF XY:

0.000960

AC XY:

698

AN XY:

726968

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33470

American (AMR)

AF:

0.0178

AC:

798

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.000459

AC:

AN:

26126

East Asian (EAS)

AF:

0.0120

AC:

476

AN:

39690

South Asian (SAS)

AF:

0.000661

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.000521

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000603

AC:

AN:

1111594

Other (OTH)

AF:

0.00177

AC:

107

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152298

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

114

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41584

American (AMR)

AF:

0.00942

AC:

144

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0130

AC:

AN:

5170

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68010

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.00264

ESP6500AA

AF:

0.000260

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00306

AC:

370

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 20, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;T;.;T;.

Eigen

Benign

0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.84

T;.;T;T;T;T

MetaRNN

Benign

0.0097

T;T;T;T;T;T

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.20

N;N;N;.;.;.

PhyloP100

0.66

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.5

N;N;N;N;.;.

REVEL

Uncertain

0.46

Sift

Benign

0.11

T;T;T;T;.;.

Sift4G

Benign

0.15

T;T;T;T;T;T

Polyphen

1.0

.;D;D;D;.;.

Vest4

0.70

MutPred

0.59

Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);Loss of MoRF binding (P = 0.0531);.;.;.;

MVP

0.77

MPC

0.28

ClinPred

0.042

GERP RS

1.9

Varity_R

0.19

gMVP

0.58

Mutation Taster

=84/16

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over