Genetic Variant CNTN5:c.3200-75A>G (chr11-100356042-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014361.4(CNTN5):c.3200-75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 920,322 control chromosomes in the GnomAD database, including 48,113 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8031 hom., cov: 32)

Exomes 𝑓: 0.31 ( 40082 hom. )

Consequence

CNTN5
NM_014361.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.964

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNTN5	NM_014361.4	MANE Select	c.3200-75A>G	intron	N/A	NP_055176.1
CNTN5	NM_001243270.2		c.3200-75A>G	intron	N/A	NP_001230199.1
CNTN5	NM_175566.2		c.2978-75A>G	intron	N/A	NP_780775.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNTN5	ENST00000524871.6	TSL:1 MANE Select	c.3200-75A>G	intron	N/A	ENSP00000435637.1
CNTN5	ENST00000418526.6	TSL:1	c.2978-75A>G	intron	N/A	ENSP00000393229.2
CNTN5	ENST00000528682.5	TSL:5	c.3200-75A>G	intron	N/A	ENSP00000436185.1

Frequencies

GnomAD3 genomes

AF:

0.319

AC:

48228

AN:

151362

Hom.:

8031

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.345

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.347

Gnomad EAS

AF:

0.0625

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.305

GnomAD4 exome

AF:

0.313

AC:

240357

AN:

768842

Hom.:

40082

AF XY:

0.309

AC XY:

124382

AN XY:

402556

show subpopulations

African (AFR)

AF:

0.330

AC:

6241

AN:

18936

American (AMR)

AF:

0.240

AC:

8395

AN:

34952

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

7448

AN:

20996

East Asian (EAS)

AF:

0.0435

AC:

1444

AN:

33218

South Asian (SAS)

AF:

0.214

AC:

14239

AN:

66518

European-Finnish (FIN)

AF:

0.334

AC:

15959

AN:

47736

Middle Eastern (MID)

AF:

0.345

AC:

1547

AN:

4488

European-Non Finnish (NFE)

AF:

0.344

AC:

173470

AN:

504704

Other (OTH)

AF:

0.311

AC:

11614

AN:

37294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

8404

16808

25212

33616

42020

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3236

6472

9708

12944

16180

<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:

0.318

AC:

48235

AN:

151480

Hom.:

8031

Cov.:

AF XY:

0.313

AC XY:

23181

AN XY:

74016

show subpopulations

African (AFR)

AF:

0.327

AC:

13528

AN:

41378

American (AMR)

AF:

0.273

AC:

4132

AN:

15138

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

1202

AN:

3466

East Asian (EAS)

AF:

0.0617

AC:

318

AN:

5152

South Asian (SAS)

AF:

0.190

AC:

917

AN:

4818

European-Finnish (FIN)

AF:

0.345

AC:

3645

AN:

10558

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23453

AN:

67660

Other (OTH)

AF:

0.302

AC:

636

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1656

3313

4969

6626

8282

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

482

964

1446

1928

2410

<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:

0.325

Hom.:

10572

Bravo

AF:

0.315

Asia WGS

AF:

0.141

AC:

491

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.64

PhyloP100

0.96

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over