19-54930534-T-C

Position:

chr19-54930534-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001405531.1(NLRP7):c.2775A>G(p.Ala925=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,607,408 control chromosomes in the GnomAD database, including 254,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 23596 hom., cov: 31)

Exomes 𝑓: 0.56 ( 231219 hom. )

Consequence

NLRP7
NM_001405531.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.83

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 links:

NCR1 (HGNC:):

NCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-54930534-T-C is Benign according to our data. Variant chr19-54930534-T-C is described in ClinVar as [Benign]. Clinvar id is 330156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-54930534-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.83 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP7	NM_001127255.2 linkuse as main transcript	c.2775A>G	p.Ala925=	synonymous_variant	9/11	ENST00000592784.6	NP_001120727.1
NLRP7	NM_001405531.1 linkuse as main transcript	c.2775A>G	p.Ala925=	synonymous_variant	11/13		NP_001392460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 linkuse as main transcript	c.2775A>G	p.Ala925=	synonymous_variant	9/11	1	NM_001127255.2	ENSP00000468706	P2	Q8WX94-3

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84170

AN:

151810

Hom.:

23574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.626

Gnomad EAS

AF:

0.716

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.551

GnomAD3 exomes

AF:

0.588

AC:

147847

AN:

251404

Hom.:

44116

AF XY:

0.589

AC XY:

80070

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.520

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.627

Gnomad EAS exome

AF:

0.716

Gnomad SAS exome

AF:

0.630

Gnomad FIN exome

AF:

0.553

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.561

AC:

817058

AN:

1455480

Hom.:

231219

Cov.:

AF XY:

0.565

AC XY:

409176

AN XY:

724438

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.628

Gnomad4 EAS exome

AF:

0.719

Gnomad4 SAS exome

AF:

0.637

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.554

AC:

84235

AN:

151928

Hom.:

23596

Cov.:

AF XY:

0.558

AC XY:

41416

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.518

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.626

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.635

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.548

Alfa

AF:

0.557

Hom.:

24432

Bravo

AF:

0.554

Asia WGS

AF:

0.619

AC:

2154

AN:

3478

EpiCase

AF:

0.555

EpiControl

AF:

0.552

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hydatidiform mole, recurrent, 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.75

DANN

Benign

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over