NM_176810.2:c.2283-168T>C

Variant names:

• chr19-55908124-A-G
• rs2117900
• NM_176810.2:c.2283-168T>C

Variant summary

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

The NM_176810.2(NLRP13):​c.2283-168T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,772 control chromosomes in the GnomAD database, including 12,163 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 0.39 (12163 hom., cov: 30)
• Consequence: NLRP13 NM_176810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0830
• Publications: 2 publications found

Genes affected

NLRP13 (HGNC:22937): (NLR family pyrin domain containing 13) 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. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP13	NM_176810.2	c.2283-168T>C		intron_variant	Intron 6 of 10	ENST00000342929.4	NP_789780.2
NLRP13	NM_001321057.1	c.2283-168T>C		intron_variant	Intron 6 of 11		NP_001307986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP13	ENST00000342929.4	c.2283-168T>C		intron_variant	Intron 6 of 10	1	NM_176810.2	ENSP00000343891.3
NLRP13	ENST00000588751.5	c.2283-168T>C		intron_variant	Intron 6 of 11	5		ENSP00000467899.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59710 AN: 151654 Hom.: 12145 Cov.: 30

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.383

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.394 AC: 59777 AN: 151772 Hom.: 12163 Cov.: 30 AF XY: 0.390 AC XY: 28915 AN XY: 74154

African (AFR) AF: 0.499 AC: 20653 AN: 41366

American (AMR) AF: 0.314 AC: 4789 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1225 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2186 AN: 5132

South Asian (SAS) AF: 0.378 AC: 1815 AN: 4802

European-Finnish (FIN) AF: 0.291 AC: 3059 AN: 10516

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24886 AN: 67920

Other (OTH) AF: 0.381 AC: 805 AN: 2112

Alfa AF: 0.372 Hom.: 18157

Bravo AF: 0.402

Asia WGS AF: 0.399 AC: 1388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		-0.083
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: rs2117900; hg19: chr19-56419490;