dbSNP rs35994137: CNTNAP4:c.1334-11C>A (chr16-76461945-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033401.5(CNTNAP4):c.1334-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,609,258 control chromosomes in the GnomAD database, including 130,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 9461 hom., cov: 31)

Exomes 𝑓: 0.40 ( 120930 hom. )

Consequence

CNTNAP4
NM_033401.5 intron

Scores

Splicing: ADA: 0.006034

Clinical Significance

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

Conservation

PhyloP100: 0.600

Publications

5 publications found

Variant links:

Genes affected

CNTNAP4 (HGNC:18747): (contactin associated protein family member 4) This gene encodes a member of the neurexin protein family. Members of this family function in the vertebrate nervous system as cell adhesion molecules and receptors. This protein contains epidermal growth factor repeats and laminin G domains. In addition, it includes an F5/8 type C domain, discoidin/neuropilin- and fibrinogen-like domains, and thrombospondin N-terminal-like domains. This protein may also play a role in proper neurotransmission in the dopaminergic and GABAergic systems and mutations in this gene may be associated with certain psychiatric illnesses. A polymorphism in an intron of this gene may be associated with longevity. [provided by RefSeq, Apr 2016]

CNTNAP4 links:

ENSG00000287694 (HGNC:):

ENSG00000287694 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 (BayesDel_noAF=-0.76).

BP6

Variant 16-76461945-C-A is Benign according to our data. Variant chr16-76461945-C-A is described in ClinVar as Benign. ClinVar VariationId is 1221600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033401.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNTNAP4	NM_033401.5	MANE Select	c.1334-11C>A	intron	N/A	NP_207837.2	Q9C0A0-1
CNTNAP4	NM_001322181.2		c.1331-11C>A	intron	N/A	NP_001309110.1
CNTNAP4	NM_001322188.2		c.1334-11C>A	intron	N/A	NP_001309117.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNTNAP4	ENST00000611870.5	TSL:1 MANE Select	c.1334-11C>A	intron	N/A	ENSP00000479811.1	Q9C0A0-1
CNTNAP4	ENST00000622250.4	TSL:1	c.1190-11C>A	intron	N/A	ENSP00000477698.1	A0A087WTA1
ENSG00000287694	ENST00000655556.1		n.1334-11C>A	intron	N/A	ENSP00000499374.1	A0A590UJB1

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49140

AN:

151936

Hom.:

9453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0963

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.389

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.331

GnomAD2 exomes

AF:

0.376

AC:

94403

AN:

250784

AF XY:

0.373

show subpopulations

Gnomad AFR exome

AF:

0.0871

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.401

AC:

583797

AN:

1457202

Hom.:

120930

Cov.:

AF XY:

0.397

AC XY:

287759

AN XY:

725146

show subpopulations

African (AFR)

AF:

0.0818

AC:

2737

AN:

33454

American (AMR)

AF:

0.426

AC:

19043

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.372

AC:

9694

AN:

26066

East Asian (EAS)

AF:

0.352

AC:

13944

AN:

39634

South Asian (SAS)

AF:

0.253

AC:

21735

AN:

86068

European-Finnish (FIN)

AF:

0.488

AC:

25986

AN:

53304

Middle Eastern (MID)

AF:

0.274

AC:

1575

AN:

5738

European-Non Finnish (NFE)

AF:

0.421

AC:

466844

AN:

1108042

Other (OTH)

AF:

0.369

AC:

22239

AN:

60200

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

14715

29429

44144

58858

73573

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14118

28236

42354

56472

70590

<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:

0.323

AC:

49163

AN:

152056

Hom.:

9461

Cov.:

AF XY:

0.327

AC XY:

24262

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0961

AC:

3991

AN:

41514

American (AMR)

AF:

0.402

AC:

6140

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3470

East Asian (EAS)

AF:

0.389

AC:

2005

AN:

5156

South Asian (SAS)

AF:

0.264

AC:

1271

AN:

4814

European-Finnish (FIN)

AF:

0.486

AC:

5126

AN:

10554

Middle Eastern (MID)

AF:

0.344

AC:

101

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28296

AN:

67966

Other (OTH)

AF:

0.328

AC:

692

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1555

3109

4664

6218

7773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.297

Hom.:

1286

Bravo

AF:

0.311

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.0

(source)

DANN

Benign

0.68

PhyloP100

0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0060

dbscSNV1_RF

Benign

0.028

SpliceAI score (max)

0.070

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