rs140769141

Variant names:

• chr19-53795933-G-A
• rs140769141
• NM_144687.4:c.3024C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-53795933-G-A
• chr19-53795933-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_144687.4(NLRP12):​c.3024C>T​(p.Asn1008Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,614,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00066 (0 hom.)
• Consequence: NLRP12 NM_144687.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.694
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 19-53795933-G-A is Benign according to our data. Variant chr19-53795933-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 330002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.694 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00127 (194/152282) while in subpopulation AFR AF = 0.00334 (139/41568). AF 95% confidence interval is 0.00289. There are 0 homozygotes in GnomAd4. There are 81 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 194 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.3024C>T	p.Asn1008Asn	synonymous	Exon 9 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.3027C>T	p.Asn1009Asn	synonymous	Exon 9 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.2853C>T	p.Asn951Asn	synonymous	Exon 8 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.3024C>T	p.Asn1008Asn	synonymous	Exon 9 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.3027C>T	p.Asn1009Asn	synonymous	Exon 9 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.2934-1797C>T		intron	N/A	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 194 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000509 AC: 128 AN: 251432 AF XY: 0.000508

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000536

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000664 AC: 971 AN: 1461854 Hom.: 0 Cov.: 32 AF XY: 0.000633 AC XY: 460 AN XY: 727222

African (AFR) AF: 0.00272 AC: 91 AN: 33478

American (AMR) AF: 0.000268 AC: 12 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000728 AC: 810 AN: 1111984

Other (OTH) AF: 0.000629 AC: 38 AN: 60392

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152282 Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74454

African (AFR) AF: 0.00334 AC: 139 AN: 41568

American (AMR) AF: 0.000196 AC: 3 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000661 AC: 45 AN: 68028

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000730 Hom.: 0

Bravo AF: 0.00134

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000533

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Familial cold autoinflammatory syndrome 2 (3)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.1
DANN	Benign	0.69
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140769141; hg19: chr19-54299187;