19-54927800-C-G

Position:

• chr19-54927800-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001127255.2(NLRP7):​c.2811-25G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,605,804 control chromosomes in the GnomAD database, including 1,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (627 hom., cov: 33)
  • Exomes 𝑓: 0.013 (1047 hom.)
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.186

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-54927800-C-G is Benign according to our data. Variant chr19-54927800-C-G is described in ClinVar as [Benign]. Clinvar id is 97770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP7	NM_001127255.2	c.2811-25G>C		intron_variant			NP_001120727.1
NLRP7	NM_001405531.1	c.2811-25G>C		intron_variant			NP_001392460.1
NLRP7	NM_139176.4	c.2727-25G>C		intron_variant			NP_631915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP7	ENST00000592784.6	c.2811-25G>C		intron_variant		1		ENSP00000468706.1

Frequencies

GnomAD3 genomes AF: 0.0597 AC: 9073 AN: 152036 Hom.: 627 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0886

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.0575

GnomAD3 exomes AF: 0.0386 AC: 9704 AN: 251258 Hom.: 587 AF XY: 0.0303 AC XY: 4118 AN XY: 135804

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.114

Gnomad SAS exome AF: 0.00356

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.00260

Gnomad OTH exome AF: 0.0264

GnomAD4 exome AF: 0.0126 AC: 18381 AN: 1453650 Hom.: 1047 Cov.: 32 AF XY: 0.0114 AC XY: 8217 AN XY: 723842

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.00219

Gnomad4 EAS exome AF: 0.0920

Gnomad4 SAS exome AF: 0.00418

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.0242

GnomAD4 genome AF: 0.0599 AC: 9108 AN: 152154 Hom.: 627 Cov.: 33 AF XY: 0.0600 AC XY: 4467 AN XY: 74428

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0889

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.00247

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0104 Hom.: 17

Bravo AF: 0.0708

Asia WGS AF: 0.0660 AC: 231 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

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

-

- -

Hydatidiform mole, recurrent, 1 Other:1

not provided, no classification provided

literature only

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs775870; hg19: chr19-55439168; COSMIC: COSV60179151;