19-54939682-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000588756.5(NLRP7):c.1137G>A(p.Lys379Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,612,666 control chromosomes in the GnomAD database, including 36,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2952 hom., cov: 31)

Exomes 𝑓: 0.21 ( 33807 hom. )

Consequence

NLRP7
ENST00000588756.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -6.88

Publications

16 publications found

Variant links:

Genes affected

NLRP7 (HGNC:22947): (NLR family pyrin domain containing 7) This gene encodes a member of the NACHT, leucine rich repeat, and PYD containing (NLRP) protein family. It has an N-terminal pyrin domain, followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region. NLRP proteins are implicated in the activation of proinflammatory caspases through multiprotein complexes called inflammasomes. This gene may act as a feedback regulator of caspase-1-dependent interleukin 1-beta secretion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NLRP7 Gene-Disease associations (from GenCC):

hydatidiform mole, recurrent, 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
complete hydatidiform mole
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NLRP7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 19-54939682-C-T is Benign according to our data. Variant chr19-54939682-C-T is described in ClinVar as Benign. ClinVar VariationId is 330172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
NLRP7	NM_001127255.2 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 4 of 11	NP_001120727.1	Q8WX94-3
NLRP7	NM_001405531.1 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 6 of 13	NP_001392460.1
NLRP7	NM_139176.4 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 4 of 11	NP_631915.2	Q8WX94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 link	c.1137G>A	p.Lys379Lys	synonymous_variant	Exon 4 of 11	1		ENSP00000468706.1		Q8WX94-3

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28674

AN:

151800

Hom.:

2948

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.239

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.202

GnomAD2 exomes

AF:

0.212

AC:

52890

AN:

249060

AF XY:

0.211

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.207

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.213

AC:

311722

AN:

1460750

Hom.:

33807

Cov.:

AF XY:

0.213

AC XY:

154719

AN XY:

726708

show subpopulations

African (AFR)

AF:

0.116

AC:

3881

AN:

33444

American (AMR)

AF:

0.294

AC:

13126

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

5579

AN:

26130

East Asian (EAS)

AF:

0.172

AC:

6821

AN:

39698

South Asian (SAS)

AF:

0.224

AC:

19307

AN:

86206

European-Finnish (FIN)

AF:

0.213

AC:

11339

AN:

53212

Middle Eastern (MID)

AF:

0.208

AC:

1072

AN:

5164

European-Non Finnish (NFE)

AF:

0.214

AC:

238192

AN:

1111904

Other (OTH)

AF:

0.206

AC:

12405

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

18945

37890

56835

75780

94725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8378

16756

25134

33512

41890

<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:

0.189

AC:

28688

AN:

151916

Hom.:

2952

Cov.:

AF XY:

0.191

AC XY:

14213

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.116

AC:

4825

AN:

41468

American (AMR)

AF:

0.273

AC:

4161

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

699

AN:

3470

East Asian (EAS)

AF:

0.168

AC:

859

AN:

5120

South Asian (SAS)

AF:

0.219

AC:

1052

AN:

4798

European-Finnish (FIN)

AF:

0.210

AC:

2225

AN:

10596

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14158

AN:

67912

Other (OTH)

AF:

0.201

AC:

422

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1106

2212

3318

4424

5530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.127

Hom.:

426

Bravo

AF:

0.189

EpiCase

AF:

0.208

EpiControl

AF:

0.211

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Hydatidiform mole, recurrent, 1

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.33

(source)

DANN

Benign

0.47

PhyloP100

-6.9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over