11-7038634-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_176822.4(NLRP14):ā€‹c.48A>Gā€‹(p.Leu16=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000555 in 1,614,010 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: š‘“ 0.00053 ( 0 hom., cov: 32)
Exomes š‘“: 0.00056 ( 6 hom. )

Consequence

NLRP14
NM_176822.4 synonymous

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.83
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 11-7038634-A-G is Benign according to our data. Variant chr11-7038634-A-G is described in ClinVar as [Benign]. Clinvar id is 3048967.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-4.83 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000558 (816/1461824) while in subpopulation EAS AF= 0.0182 (722/39698). AF 95% confidence interval is 0.0171. There are 6 homozygotes in gnomad4_exome. There are 413 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NLRP14NM_176822.4 linkuse as main transcriptc.48A>G p.Leu16= synonymous_variant 2/12 ENST00000299481.5 NP_789792.1
NLRP14XM_011520044.2 linkuse as main transcriptc.48A>G p.Leu16= synonymous_variant 2/11 XP_011518346.1
NLRP14XM_047426867.1 linkuse as main transcriptc.48A>G p.Leu16= synonymous_variant 2/11 XP_047282823.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NLRP14ENST00000299481.5 linkuse as main transcriptc.48A>G p.Leu16= synonymous_variant 2/125 NM_176822.4 ENSP00000299481 P1

Frequencies

GnomAD3 genomes
AF:
0.000526
AC:
80
AN:
152070
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0150
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00150
AC:
377
AN:
251354
Hom.:
4
AF XY:
0.00139
AC XY:
189
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0194
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000816
GnomAD4 exome
AF:
0.000558
AC:
816
AN:
1461824
Hom.:
6
Cov.:
32
AF XY:
0.000568
AC XY:
413
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0182
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000762
GnomAD4 genome
AF:
0.000526
AC:
80
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.000565
AC XY:
42
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0151
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000754
Hom.:
0
Bravo
AF:
0.000910
Asia WGS
AF:
0.00549
AC:
19
AN:
3476
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

NLRP14-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 09, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.15
DANN
Benign
0.47

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138272571; hg19: chr11-7059865; API