chr19-54930401-G-A

Variant names:

• chr19-54930401-G-A
• rs269949
• NM_001127255.2:c.2810+98C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127255.2(NLRP7):​c.2810+98C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 812,880 control chromosomes in the GnomAD database, including 132,608 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (23304 hom., cov: 30)
  • Exomes 𝑓: 0.57 (109304 hom.)
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.30
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP7	NM_001127255.2	MANE Select	c.2810+98C>T		intron	N/A	NP_001120727.1
	NLRP7	NM_001405531.1		c.2810+98C>T		intron	N/A	NP_001392460.1
	NLRP7	NM_139176.4		c.2726+98C>T		intron	N/A	NP_631915.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP7	ENST00000592784.6	TSL:1 MANE Select	c.2810+98C>T		intron	N/A	ENSP00000468706.1
	NLRP7	ENST00000588756.5	TSL:1	c.2810+98C>T		intron	N/A	ENSP00000467123.1
	NLRP7	ENST00000340844.6	TSL:1	c.2810+98C>T		intron	N/A	ENSP00000339491.2

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83571 AN: 151146 Hom.: 23281 Cov.: 30

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.548

GnomAD4 exome AF: 0.569 AC: 376241 AN: 661614 Hom.: 109304 AF XY: 0.573 AC XY: 202825 AN XY: 353876

African (AFR) AF: 0.514 AC: 9242 AN: 17986

American (AMR) AF: 0.634 AC: 22398 AN: 35354

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 12755 AN: 20328

East Asian (EAS) AF: 0.719 AC: 24137 AN: 33590

South Asian (SAS) AF: 0.637 AC: 42288 AN: 66338

European-Finnish (FIN) AF: 0.547 AC: 19700 AN: 35982

Middle Eastern (MID) AF: 0.612 AC: 1710 AN: 2796

European-Non Finnish (NFE) AF: 0.541 AC: 224679 AN: 415292

Other (OTH) AF: 0.569 AC: 19332 AN: 33948

GnomAD4 genome AF: 0.553 AC: 83638 AN: 151266 Hom.: 23304 Cov.: 30 AF XY: 0.556 AC XY: 41109 AN XY: 73904

African (AFR) AF: 0.517 AC: 21308 AN: 41230

American (AMR) AF: 0.577 AC: 8781 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2164 AN: 3454

East Asian (EAS) AF: 0.714 AC: 3638 AN: 5092

South Asian (SAS) AF: 0.635 AC: 3049 AN: 4802

European-Finnish (FIN) AF: 0.551 AC: 5798 AN: 10516

Middle Eastern (MID) AF: 0.572 AC: 166 AN: 290

European-Non Finnish (NFE) AF: 0.552 AC: 37330 AN: 67658

Other (OTH) AF: 0.545 AC: 1144 AN: 2098

Alfa AF: 0.556 Hom.: 38859

Bravo AF: 0.554

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.84
DANN	Benign	0.67
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs269949; hg19: chr19-55441769;