Genetic Variant PCDH1:c.*80G>A (chr5-141863068-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001278613.2(PCDH1):c.*80G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,364,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

PCDH1
NM_001278613.2 3_prime_UTR

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278613.2. 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>A	intron	N/A	NP_115796.2
PCDH1	NM_001278613.2		c.*80G>A	3_prime_UTR	Exon 3 of 3	NP_001265542.1
PCDH1	NM_002587.5		c.*80G>A	3_prime_UTR	Exon 3 of 3	NP_002578.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PCDH1	ENST00000394536.4	TSL:1	c.*80G>A	3_prime_UTR	Exon 3 of 3	ENSP00000378043.3	Q08174-1
PCDH1	ENST00000287008.8	TSL:5 MANE Select	c.3099+164G>A	intron	N/A	ENSP00000287008.3	Q08174-2
PCDH1	ENST00000511044.1	TSL:1	n.2491G>A	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000158

AC:

192

AN:

1212886

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

104

AN XY:

579554

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27584

American (AMR)

AF:

0.00

AC:

AN:

15518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17258

East Asian (EAS)

AF:

0.0000603

AC:

AN:

33160

South Asian (SAS)

AF:

0.00

AC:

AN:

38878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39984

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3582

European-Non Finnish (NFE)

AF:

0.000186

AC:

184

AN:

986946

Other (OTH)

AF:

0.000120

AC:

AN:

49976

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000526

AC:

AN:

151952

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41378

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00

Hom.:

174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.030

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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