rs775882

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127255.2(NLRP7):c.955G>A(p.Val319Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,596 control chromosomes in the GnomAD database, including 46,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7509 hom., cov: 31)

Exomes 𝑓: 0.23 ( 38636 hom. )

Consequence

NLRP7
NM_001127255.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.31

Publications

28 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.873672E-4).

BP6

Variant 19-54939864-C-T is Benign according to our data. Variant chr19-54939864-C-T is described in ClinVar as Benign. ClinVar VariationId is 330176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127255.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLRP7	NM_001127255.2	MANE Select	c.955G>A	p.Val319Ile	missense	Exon 4 of 11	NP_001120727.1	Q8WX94-3
NLRP7	NM_001405531.1		c.955G>A	p.Val319Ile	missense	Exon 6 of 13	NP_001392460.1	Q8WX94-3
NLRP7	NM_139176.4		c.955G>A	p.Val319Ile	missense	Exon 4 of 11	NP_631915.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NLRP7	ENST00000592784.6	TSL:1 MANE Select	c.955G>A	p.Val319Ile	missense	Exon 4 of 11	ENSP00000468706.1	Q8WX94-3
NLRP7	ENST00000588756.5	TSL:1	c.955G>A	p.Val319Ile	missense	Exon 6 of 13	ENSP00000467123.1	Q8WX94-3
NLRP7	ENST00000340844.6	TSL:1	c.955G>A	p.Val319Ile	missense	Exon 4 of 10	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44178

AN:

151846

Hom.:

7478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.238

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.287

GnomAD2 exomes

AF:

0.241

AC:

60578

AN:

251130

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.471

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.213

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.225

AC:

329397

AN:

1461632

Hom.:

38636

Cov.:

AF XY:

0.224

AC XY:

162574

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.469

AC:

15699

AN:

33476

American (AMR)

AF:

0.322

AC:

14381

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5817

AN:

26134

East Asian (EAS)

AF:

0.173

AC:

6869

AN:

39698

South Asian (SAS)

AF:

0.229

AC:

19780

AN:

86254

European-Finnish (FIN)

AF:

0.213

AC:

11387

AN:

53408

Middle Eastern (MID)

AF:

0.248

AC:

1433

AN:

5768

European-Non Finnish (NFE)

AF:

0.216

AC:

239885

AN:

1111804

Other (OTH)

AF:

0.234

AC:

14146

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

19607

39214

58822

78429

98036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8588

17176

25764

34352

42940

<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:

0.291

AC:

44264

AN:

151964

Hom.:

7509

Cov.:

AF XY:

0.290

AC XY:

21563

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.463

AC:

19177

AN:

41430

American (AMR)

AF:

0.322

AC:

4906

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

723

AN:

3470

East Asian (EAS)

AF:

0.172

AC:

888

AN:

5164

South Asian (SAS)

AF:

0.228

AC:

1099

AN:

4820

European-Finnish (FIN)

AF:

0.210

AC:

2220

AN:

10576

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14354

AN:

67954

Other (OTH)

AF:

0.285

AC:

601

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1427

2854

4282

5709

7136

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.226

Hom.:

10733

Bravo

AF:

0.306

TwinsUK

AF:

0.221

AC:

819

ALSPAC

AF:

0.211

AC:

815

ESP6500AA

AF:

0.462

AC:

2034

ESP6500EA

AF:

0.210

AC:

1808

ExAC

AF:

0.241

AC:

29263

Asia WGS

AF:

0.249

AC:

867

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.214

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hydatidiform mole, recurrent, 1 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0090

(source)

DANN

Benign

0.14

DEOGEN2

Benign

0.033

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0055

MetaRNN

Benign

0.00019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.015

PhyloP100

-1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.050

REVEL

Benign

0.095

Sift

Benign

0.94

Sift4G

Benign

1.0

Polyphen

0.0040

Vest4

0.015

MPC

0.21

ClinPred

0.00072

GERP RS

-3.1

Varity_R

0.025

gMVP

0.12

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