rs185571043

Variant names:

• chr19-53793877-G-A
• rs185571043
• NM_144687.4:c.*172C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-53793877-G-A
• chr19-53793877-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_144687.4(NLRP12):​c.*172C>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 0.0000735 in 693,936 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: NLRP12 NM_144687.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-53793877-G-A is Benign according to our data. Variant chr19-53793877-G-A is described in ClinVar as Benign. ClinVar VariationId is 894484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 15 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.*172C>T		3_prime_UTR	Exon 10 of 10	NP_653288.1	P59046-1
	NLRP12	NM_001277126.2		c.*172C>T		3_prime_UTR	Exon 10 of 10	NP_001264055.1	P59046-7
	NLRP12	NM_001277129.1		c.*172C>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.*172C>T		3_prime_UTR	Exon 10 of 10	ENSP00000319377.6	P59046-1
	NLRP12	ENST00000391773.8	TSL:1	c.*172C>T		3_prime_UTR	Exon 10 of 10	ENSP00000375653.1	P59046-7
	NLRP12	ENST00000345770.9	TSL:1	c.*172C>T		3_prime_UTR	Exon 9 of 9	ENSP00000341428.5	A0A0C4DH17

Frequencies

GnomAD3 genomes AF: 0.0000989 AC: 15 AN: 151704 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000315

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000664 AC: 36 AN: 542114 Hom.: 0 Cov.: 5 AF XY: 0.0000582 AC XY: 17 AN XY: 292344

African (AFR) AF: 0.000388 AC: 6 AN: 15472

American (AMR) AF: 0.0000883 AC: 3 AN: 33982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19146

East Asian (EAS) AF: 0.00 AC: 0 AN: 31892

South Asian (SAS) AF: 0.0000164 AC: 1 AN: 60972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2516

European-Non Finnish (NFE) AF: 0.0000804 AC: 25 AN: 310974

Other (OTH) AF: 0.0000335 AC: 1 AN: 29872

GnomAD4 genome AF: 0.0000988 AC: 15 AN: 151822 Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6 AN XY: 74160

African (AFR) AF: 0.000314 AC: 13 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15200

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.0000818 Hom.: 0

Bravo AF: 0.000102

ClinVar

ClinVar submissions as Germline

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	-0.93
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.22

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: rs185571043; hg19: chr19-54297131;