19-53793845-G-A

Variant names:

• chr19-53793845-G-A
• rs141410784
• NM_144687.4:c.*204C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_144687.4(NLRP12):​c.*204C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 645,344 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18
• Publications: 0 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 19-53793845-G-A is Benign according to our data. Variant chr19-53793845-G-A is described in ClinVar as Benign. ClinVar VariationId is 329992.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00402 (610/151798) while in subpopulation AFR AF = 0.0137 (567/41420). AF 95% confidence interval is 0.0128. There are 4 homozygotes in GnomAd4. There are 288 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 610 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144687.4. 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
	NLRP12	NM_144687.4	MANE Select	c.*204C>T		3_prime_UTR	Exon 10 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.*204C>T		3_prime_UTR	Exon 10 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.*204C>T		3_prime_UTR	Exon 9 of 9	NP_001264058.1	P59046-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP12	ENST00000324134.11	TSL:1 MANE Select	c.*204C>T		3_prime_UTR	Exon 10 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.*204C>T		3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.*204C>T		3_prime_UTR	Exon 9 of 9	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.00401 AC: 608 AN: 151680 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00251

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00192

GnomAD4 exome AF: 0.000505 AC: 249 AN: 493546 Hom.: 1 Cov.: 3 AF XY: 0.000406 AC XY: 107 AN XY: 263526

African (AFR) AF: 0.0133 AC: 190 AN: 14254

American (AMR) AF: 0.00110 AC: 32 AN: 29144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16404

East Asian (EAS) AF: 0.0000321 AC: 1 AN: 31116

South Asian (SAS) AF: 0.0000374 AC: 2 AN: 53522

European-Finnish (FIN) AF: 0.0000313 AC: 1 AN: 31904

Middle Eastern (MID) AF: 0.000463 AC: 1 AN: 2158

European-Non Finnish (NFE) AF: 0.00000348 AC: 1 AN: 287272

Other (OTH) AF: 0.000756 AC: 21 AN: 27772

GnomAD4 genome AF: 0.00402 AC: 610 AN: 151798 Hom.: 4 Cov.: 31 AF XY: 0.00388 AC XY: 288 AN XY: 74180

African (AFR) AF: 0.0137 AC: 567 AN: 41420

American (AMR) AF: 0.00250 AC: 38 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67940

Other (OTH) AF: 0.00190 AC: 4 AN: 2102

Alfa AF: 0.00352 Hom.: 1

Bravo AF: 0.00432

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Familial cold autoinflammatory syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.34
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs141410784; hg19: chr19-54297099;