Variant 19-54927798-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127255.2(NLRP7):c.2811-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 1,605,672 control chromosomes in the GnomAD database, including 254,459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 23702 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230757 hom. )

Consequence

NLRP7
NM_001127255.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.672

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:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [provided by Alliance of Genome Resources, Apr 2022]

NCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 19-54927798-T-C is Benign according to our data. Variant chr19-54927798-T-C is described in ClinVar as [Benign]. Clinvar id is 997711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
NLRP7	NM_001127255.2 linkuse as main transcript	c.2811-23A>G	intron_variant	NP_001120727.1	Q8WX94-3
NLRP7	NM_001405531.1 linkuse as main transcript	c.2811-23A>G	intron_variant	NP_001392460.1
NLRP7	NM_139176.4 linkuse as main transcript	c.2727-23A>G	intron_variant	NP_631915.2	Q8WX94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6 linkuse as main transcript	c.2811-23A>G		intron_variant		1		ENSP00000468706.1		Q8WX94-3

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84369

AN:

151888

Hom.:

23681

Cov.:

show subpopulations

Gnomad AFR

AF:

0.523

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.619

Gnomad EAS

AF:

0.715

Gnomad SAS

AF:

0.634

Gnomad FIN

AF:

0.552

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.549

GnomAD3 exomes

AF:

0.587

AC:

147604

AN:

251264

Hom.:

44016

AF XY:

0.589

AC XY:

79938

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.524

Gnomad AMR exome

AF:

0.645

Gnomad ASJ exome

AF:

0.621

Gnomad EAS exome

AF:

0.715

Gnomad SAS exome

AF:

0.628

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.564

GnomAD4 exome

AF:

0.561

AC:

815427

AN:

1453668

Hom.:

230757

Cov.:

AF XY:

0.564

AC XY:

408352

AN XY:

723556

show subpopulations

Gnomad4 AFR exome

AF:

0.515

Gnomad4 AMR exome

AF:

0.639

Gnomad4 ASJ exome

AF:

0.621

Gnomad4 EAS exome

AF:

0.719

Gnomad4 SAS exome

AF:

0.635

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.546

Gnomad4 OTH exome

AF:

0.573

GnomAD4 genome

AF:

0.555

AC:

84433

AN:

152004

Hom.:

23702

Cov.:

AF XY:

0.559

AC XY:

41515

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.523

Gnomad4 AMR

AF:

0.579

Gnomad4 ASJ

AF:

0.619

Gnomad4 EAS

AF:

0.717

Gnomad4 SAS

AF:

0.634

Gnomad4 FIN

AF:

0.552

Gnomad4 NFE

AF:

0.553

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.565

Hom.:

4908

Bravo

AF:

0.555

Asia WGS

AF:

0.618

AC:

2152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hydatidiform mole

Benign:1

Benign, criteria provided, single submitter

research

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Feb 22, 2021

- -

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

-0.99

CADD

Benign

0.32

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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