rs12801277

Variant names:

• chr11-7038729-A-C
• rs12801277
• NM_176822.4:c.143A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-7038729-A-C
• chr11-7038729-A-G
• chr11-7038729-A-T

Variant summary

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

The NM_176822.4(NLRP14):​c.143A>C​(p.Asn48Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.994 in 1,614,088 control chromosomes in the GnomAD database, including 798,171 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N48K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.97 (71622 hom., cov: 31)
  • Exomes 𝑓: 1.0 (726549 hom.)
• Consequence: NLRP14 NM_176822.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0930
• Publications: 23 publications found

Genes affected

NLRP14 (HGNC:22939): (NLR family pyrin domain containing 14) The protein encoded by this gene belongs to the NALP protein family. Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). This protein may play a regulatory role in the innate immune system as similar family members belong to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7445806E-7).
• BP6: Variant 11-7038729-A-C is Benign according to our data. Variant chr11-7038729-A-C is described in ClinVar as Benign. ClinVar VariationId is 1234647.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176822.4. 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
	NLRP14	NM_176822.4	MANE Select	c.143A>C	p.Asn48Thr	missense	Exon 2 of 12	NP_789792.1	Q86W24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRP14	ENST00000299481.5	TSL:5 MANE Select	c.143A>C	p.Asn48Thr	missense	Exon 2 of 12	ENSP00000299481.5	Q86W24
	NLRP14	ENST00000892206.1		c.143A>C	p.Asn48Thr	missense	Exon 2 of 11	ENSP00000562265.1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147404 AN: 152122 Hom.: 71577 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.980

GnomAD2 exomes AF: 0.991 AC: 249068 AN: 251224 AF XY: 0.994

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.995

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.997 AC: 1457252 AN: 1461848 Hom.: 726549 Cov.: 50 AF XY: 0.997 AC XY: 725327 AN XY: 727228

African (AFR) AF: 0.889 AC: 29764 AN: 33480

American (AMR) AF: 0.994 AC: 44460 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26135 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39700 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86241 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53418 AN: 53418

Middle Eastern (MID) AF: 0.997 AC: 5749 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111774 AN: 1111972

Other (OTH) AF: 0.994 AC: 60011 AN: 60392

GnomAD4 genome AF: 0.969 AC: 147506 AN: 152240 Hom.: 71622 Cov.: 31 AF XY: 0.969 AC XY: 72143 AN XY: 74438

African (AFR) AF: 0.891 AC: 36998 AN: 41508

American (AMR) AF: 0.990 AC: 15141 AN: 15300

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4816 AN: 4816

European-Finnish (FIN) AF: 1.00 AC: 10620 AN: 10620

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68013 AN: 68036

Other (OTH) AF: 0.980 AC: 2064 AN: 2106

Alfa AF: 0.988 Hom.: 156517

Bravo AF: 0.964

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.894 AC: 3934

ESP6500EA AF: 1.00 AC: 8588

ExAC AF: 0.990 AC: 120144

Asia WGS AF: 0.995 AC: 3459 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	NLRP14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.65
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	5.7e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-2.6	N
PhyloP100		0.093
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.2	N
REVEL	Benign	0.067
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.018
ClinPred		0.017	T
GERP RS		2.4
Varity_R		0.18
gMVP		0.11
Mutation Taster		=91/9	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: rs12801277; hg19: chr11-7059960; COSMIC: COSV107345080;