Genetic Variant PCDH1:n.2491G>C (chr5-141863068-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000511044.1(PCDH1):n.2491G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 1,364,656 control chromosomes in the GnomAD database, including 31,231 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 0.18 ( 2610 hom., cov: 31)

Exomes 𝑓: 0.21 ( 28621 hom. )

Consequence

PCDH1
ENST00000511044.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

7 publications found

Variant links:

Genes affected

PCDH1 (HGNC:8655): (protocadherin 1) This gene belongs to the protocadherin subfamily within the cadherin superfamily. The encoded protein is a membrane protein found at cell-cell boundaries. It is involved in neural cell adhesion, suggesting a possible role in neuronal development. The protein includes an extracelllular region, containing 7 cadherin-like domains, a transmembrane region and a C-terminal cytoplasmic region. Cells expressing the protein showed cell aggregation activity. Alternative splicing occurs in this gene. [provided by RefSeq, Jul 2008]

PCDH1 links:

Genome browser will be placed here

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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511044.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PCDH1	NM_032420.5	MANE Select	c.3099+164G>C	intron	N/A	NP_115796.2
PCDH1	NM_001278613.2		c.*80G>C	3_prime_UTR	Exon 3 of 3	NP_001265542.1
PCDH1	NM_002587.5		c.*80G>C	3_prime_UTR	Exon 3 of 3	NP_002578.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PCDH1	ENST00000511044.1	TSL:1	n.2491G>C	non_coding_transcript_exon	Exon 2 of 2
PCDH1	ENST00000394536.4	TSL:1	c.*80G>C	3_prime_UTR	Exon 3 of 3	ENSP00000378043.3
PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.3099+164G>C	intron	N/A	ENSP00000287008.3

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26792

AN:

151922

Hom.:

2609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0862

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.181

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.214

AC:

259510

AN:

1212616

Hom.:

28621

Cov.:

AF XY:

0.213

AC XY:

123643

AN XY:

579418

show subpopulations

African (AFR)

AF:

0.0793

AC:

2186

AN:

27582

American (AMR)

AF:

0.222

AC:

3438

AN:

15500

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

1912

AN:

17250

East Asian (EAS)

AF:

0.191

AC:

6334

AN:

33156

South Asian (SAS)

AF:

0.122

AC:

4742

AN:

38842

European-Finnish (FIN)

AF:

0.224

AC:

8942

AN:

39948

Middle Eastern (MID)

AF:

0.130

AC:

466

AN:

3582

European-Non Finnish (NFE)

AF:

0.225

AC:

221952

AN:

986794

Other (OTH)

AF:

0.191

AC:

9538

AN:

49962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

10980

21960

32940

43920

54900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8288

16576

24864

33152

41440

<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:

0.176

AC:

26795

AN:

152040

Hom.:

2610

Cov.:

AF XY:

0.175

AC XY:

13027

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.0862

AC:

3575

AN:

41496

American (AMR)

AF:

0.194

AC:

2966

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

397

AN:

3472

East Asian (EAS)

AF:

0.181

AC:

930

AN:

5140

South Asian (SAS)

AF:

0.122

AC:

589

AN:

4818

European-Finnish (FIN)

AF:

0.231

AC:

2440

AN:

10556

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15332

AN:

67962

Other (OTH)

AF:

0.167

AC:

352

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1112

2224

3337

4449

5561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<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:

0.102

Hom.:

174

Bravo

AF:

0.170

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.7

(source)

DANN

Benign

0.79

PhyloP100

-0.030

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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