dbSNP rs8056505: PYCARD:c.-887G>A (chr16-31203577-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000561508.1(PYCARD):c.-887G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 152,020 control chromosomes in the GnomAD database, including 28,976 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 0.61 ( 28976 hom., cov: 32)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

PYCARD
ENST00000561508.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.204

Publications

21 publications found

Variant links:

Genes affected

PYCARD (HGNC:16608): (PYD and CARD domain containing) This gene encodes an adaptor protein that is composed of two protein-protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PYCARD links:

PYCARD-AS1 (HGNC:45036): (PYCARD antisense RNA 1)

PYCARD-AS1 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000561508.1. 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
	PYCARD-AS1	NR_102400.1		n.*125C>T		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PYCARD	ENST00000561508.1	TSL:3	c.-887G>A	upstream_gene	N/A	ENSP00000455141.1
PYCARD-AS1	ENST00000561916.3	TSL:2	n.*125C>T	downstream_gene	N/A
PYCARD-AS1	ENST00000812284.1		n.*174C>T	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.609

AC:

92473

AN:

151894

Hom.:

28984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.616

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.450

Gnomad FIN

AF:

0.623

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.681

Gnomad OTH

AF:

0.669

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.608

AC:

92486

AN:

152012

Hom.:

28976

Cov.:

AF XY:

0.606

AC XY:

44987

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.461

AC:

19105

AN:

41420

American (AMR)

AF:

0.616

AC:

9410

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2692

AN:

3470

East Asian (EAS)

AF:

0.757

AC:

3920

AN:

5176

South Asian (SAS)

AF:

0.450

AC:

2167

AN:

4816

European-Finnish (FIN)

AF:

0.623

AC:

6583

AN:

10562

Middle Eastern (MID)

AF:

0.806

AC:

237

AN:

294

European-Non Finnish (NFE)

AF:

0.681

AC:

46272

AN:

67972

Other (OTH)

AF:

0.663

AC:

1401

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1776

3552

5329

7105

8881

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.647

Hom.:

20012

Bravo

AF:

0.609

Asia WGS

AF:

0.567

AC:

1976

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.0

(source)

DANN

Benign

0.64

PhyloP100

0.20

PromoterAI

-0.0057

Neutral

(source)

Splicing

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