NM_144687.4:c.-140T>C

Variant names:

• chr19-53824314-A-G
• rs4419163
• NM_144687.4:c.-140T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144687.4(NLRP12):​c.-140T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NLRP12 NM_144687.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 11 publications found

Genes affected

NLRP12 (HGNC:22938): (NLR family pyrin domain containing 12) This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

NLRP12 Gene-Disease associations (from GenCC):

• familial cold autoinflammatory syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRP12	NM_144687.4	c.-140T>C		5_prime_UTR_variant	Exon 1 of 10	ENST00000324134.11	NP_653288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRP12	ENST00000324134.11	c.-140T>C		5_prime_UTR_variant	Exon 1 of 10	1	NM_144687.4	ENSP00000319377.6
NLRP12	ENST00000345770.9	c.-140T>C		5_prime_UTR_variant	Exon 1 of 9	1		ENSP00000341428.5
NLRP12	ENST00000391772.1	c.-140T>C		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000375652.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151884 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 662548 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 346854

African (AFR) AF: 0.00 AC: 0 AN: 18268

American (AMR) AF: 0.00 AC: 0 AN: 31244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18680

East Asian (EAS) AF: 0.00 AC: 0 AN: 32314

South Asian (SAS) AF: 0.00 AC: 0 AN: 63238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 428494

Other (OTH) AF: 0.00 AC: 0 AN: 33450

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74158

African (AFR) AF: 0.00 AC: 0 AN: 41328

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 4858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.67
DANN	Benign	0.49
PhyloP100		-2.4
PromoterAI		0.11	Neutral

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: rs4419163; hg19: chr19-54327568;