Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001201380.3(CNTNAP3B):c.1844delT(p.Leu615ArgfsTer10) variant causes a frameshift change. The variant allele was found at a frequency of 0.00348 in 151,468 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0035 ( 0 hom., cov: 48)

Exomes 𝑓: 0.0047 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNTNAP3B
NM_001201380.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.32

Publications

0 publications found

Variant links:

Genes affected

CNTNAP3B (HGNC:32035): (contactin associated protein family member 3B) Predicted to be involved in cell adhesion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CNTNAP3B links:

ENSG00000297510 (HGNC:):

ENSG00000297510 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 9-41960804-CA-C is Benign according to our data. Variant chr9-41960804-CA-C is described in ClinVar as Benign. ClinVar VariationId is 402551.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201380.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTNAP3B	NM_001201380.3	MANE Select	c.1844delT	p.Leu615ArgfsTer10	frameshift	Exon 12 of 24	NP_001188309.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CNTNAP3B	ENST00000377561.7	TSL:1 MANE Select	c.1844delT	p.Leu615ArgfsTer10	frameshift	Exon 12 of 24	ENSP00000478671.2
CNTNAP3B	ENST00000612828.4	TSL:1	c.1844delT	p.Leu615ArgfsTer10	frameshift	Exon 12 of 23	ENSP00000483830.1
CNTNAP3B	ENST00000618777.4	TSL:1	n.1990delT		non_coding_transcript_exon	Exon 12 of 20

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

530

AN:

151348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00243

Gnomad ASJ

AF:

0.0286

Gnomad EAS

AF:

0.00568

Gnomad SAS

AF:

0.0432

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00434

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00466

AC:

6718

AN:

1442056

Hom.:

Cov.:

AF XY:

0.00577

AC XY:

4133

AN XY:

715978

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000577

AC:

AN:

32956

American (AMR)

AF:

0.00201

AC:

AN:

42766

Ashkenazi Jewish (ASJ)

AF:

0.0229

AC:

567

AN:

24800

East Asian (EAS)

AF:

0.0131

AC:

500

AN:

38202

South Asian (SAS)

AF:

0.0387

AC:

3099

AN:

80156

European-Finnish (FIN)

AF:

0.000226

AC:

AN:

53152

Middle Eastern (MID)

AF:

0.0169

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00179

AC:

1976

AN:

1105136

Other (OTH)

AF:

0.00615

AC:

365

AN:

59318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.259

Heterozygous variant carriers

839

1678

2517

3356

4195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

108

216

324

432

540

<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:

0.00348

AC:

527

AN:

151468

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

319

AN XY:

73968

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000433

AC:

AN:

41558

American (AMR)

AF:

0.00243

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0286

AC:

AN:

3352

East Asian (EAS)

AF:

0.00569

AC:

AN:

5094

South Asian (SAS)

AF:

0.0425

AC:

193

AN:

4536

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00210

AC:

142

AN:

67772

Other (OTH)

AF:

0.00429

AC:

AN:

2096

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.261

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00645

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs375643696

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over