NM_001127255.2:c.2981+123T>C

Variant names:

• chr19-54927482-A-G
• rs269932
• NM_001127255.2:c.2981+123T>C

Variant summary

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

The NM_001127255.2(NLRP7):​c.2981+123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 150,932 control chromosomes in the GnomAD database, including 23,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.56 (23349 hom., cov: 31)
  • Exomes 𝑓: 0.57 (117499 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP7 NM_001127255.2 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.146
• Publications: 2 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 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.2981+123T>C		intron	N/A	NP_001120727.1	Q8WX94-3
	NLRP7	NM_001405531.1		c.2981+123T>C		intron	N/A	NP_001392460.1	Q8WX94-3
	NLRP7	NM_139176.4		c.2897+123T>C		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.2981+123T>C		intron	N/A	ENSP00000468706.1	Q8WX94-3
	NLRP7	ENST00000588756.5	TSL:1	c.2981+123T>C		intron	N/A	ENSP00000467123.1	Q8WX94-3
	NLRP7	ENST00000340844.6	TSL:1	c.2810+3017T>C		intron	N/A	ENSP00000339491.2	Q8WX94-1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 83714 AN: 150816 Hom.: 23328 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.718

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.548

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.569 AC: 407233 AN: 716218 Hom.: 117499 AF XY: 0.573 AC XY: 218256 AN XY: 380790

African (AFR) AF: 0.517 AC: 9415 AN: 18228

American (AMR) AF: 0.640 AC: 22706 AN: 35502

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 12806 AN: 20570

East Asian (EAS) AF: 0.721 AC: 24831 AN: 34416

South Asian (SAS) AF: 0.638 AC: 42093 AN: 65990

European-Finnish (FIN) AF: 0.553 AC: 20429 AN: 36968

Middle Eastern (MID) AF: 0.627 AC: 2221 AN: 3540

European-Non Finnish (NFE) AF: 0.542 AC: 252274 AN: 465126

Other (OTH) AF: 0.570 AC: 20458 AN: 35878

GnomAD4 genome AF: 0.555 AC: 83778 AN: 150932 Hom.: 23349 Cov.: 31 AF XY: 0.558 AC XY: 41174 AN XY: 73744

African (AFR) AF: 0.522 AC: 21453 AN: 41104

American (AMR) AF: 0.579 AC: 8768 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2130 AN: 3452

East Asian (EAS) AF: 0.719 AC: 3663 AN: 5098

South Asian (SAS) AF: 0.634 AC: 3039 AN: 4790

European-Finnish (FIN) AF: 0.550 AC: 5748 AN: 10446

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37408 AN: 67614

Other (OTH) AF: 0.546 AC: 1142 AN: 2092

Alfa AF: 0.555 Hom.: 2796

Bravo AF: 0.555

Asia WGS AF: 0.618 AC: 2151 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	Hydatidiform mole, recurrent, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.4
DANN	Benign	0.60
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs269932; hg19: chr19-55438850;