chr19-53793783-C-A

Variant names:

• chr19-53793783-C-A
• rs10409778
• NM_144687.4:c.*266G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144687.4(NLRP12):​c.*266G>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 0.0655 in 548,544 control chromosomes in the GnomAD database, including 1,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (340 hom., cov: 30)
  • Exomes 𝑓: 0.069 (1396 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-53793783-C-A is Benign according to our data. Variant chr19-53793783-C-A is described in ClinVar as Benign. ClinVar VariationId is 329990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

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.*266G>T		3_prime_UTR	Exon 10 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.*266G>T		3_prime_UTR	Exon 10 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.*266G>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.*266G>T		3_prime_UTR	Exon 10 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.*266G>T		3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.*266G>T		3_prime_UTR	Exon 9 of 9	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8722 AN: 151670 Hom.: 338 Cov.: 30

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.0736

Gnomad AMR AF: 0.0494

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0209

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0551

Gnomad OTH AF: 0.0525

GnomAD4 exome AF: 0.0685 AC: 27192 AN: 396756 Hom.: 1396 Cov.: 0 AF XY: 0.0732 AC XY: 15424 AN XY: 210728

African (AFR) AF: 0.0543 AC: 608 AN: 11206

American (AMR) AF: 0.0415 AC: 714 AN: 17206

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 194 AN: 11976

East Asian (EAS) AF: 0.135 AC: 3524 AN: 26040

South Asian (SAS) AF: 0.158 AC: 7070 AN: 44668

European-Finnish (FIN) AF: 0.0234 AC: 577 AN: 24672

Middle Eastern (MID) AF: 0.0445 AC: 74 AN: 1664

European-Non Finnish (NFE) AF: 0.0549 AC: 12993 AN: 236612

Other (OTH) AF: 0.0633 AC: 1438 AN: 22712

GnomAD4 genome AF: 0.0576 AC: 8744 AN: 151788 Hom.: 340 Cov.: 30 AF XY: 0.0579 AC XY: 4291 AN XY: 74166

African (AFR) AF: 0.0535 AC: 2217 AN: 41406

American (AMR) AF: 0.0494 AC: 751 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3466

East Asian (EAS) AF: 0.144 AC: 738 AN: 5122

South Asian (SAS) AF: 0.175 AC: 840 AN: 4788

European-Finnish (FIN) AF: 0.0209 AC: 221 AN: 10574

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3742 AN: 67932

Other (OTH) AF: 0.0567 AC: 119 AN: 2098

Alfa AF: 0.0535 Hom.: 32

Bravo AF: 0.0552

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Familial cold autoinflammatory syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.45
PhyloP100		0.38
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: rs10409778; hg19: chr19-54297037;