Genetic Variant NLRP14:c.289+131delG (chr11-7039005-TG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_176822.4(NLRP14):c.289+131delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 848,710 control chromosomes in the GnomAD database, including 176,586 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.62 ( 29675 hom., cov: 0)

Exomes 𝑓: 0.65 ( 146911 hom. )

Consequence

NLRP14
NM_176822.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.810

Publications

0 publications found

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]

NLRP14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 11-7039005-TG-T is Benign according to our data. Variant chr11-7039005-TG-T is described in ClinVar as Benign. ClinVar VariationId is 1278365.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 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.289+131delG		intron	N/A	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.289+131delG		intron	N/A	ENSP00000299481.5	Q86W24
	NLRP14	ENST00000892206.1		c.289+131delG		intron	N/A	ENSP00000562265.1

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94381

AN:

151682

Hom.:

29653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.541

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.629

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.738

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.727

Gnomad MID

AF:

0.621

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.648

AC:

451932

AN:

696910

Hom.:

146911

AF XY:

0.649

AC XY:

231193

AN XY:

356428

show subpopulations

African (AFR)

AF:

0.544

AC:

9330

AN:

17166

American (AMR)

AF:

0.620

AC:

11738

AN:

18936

Ashkenazi Jewish (ASJ)

AF:

0.648

AC:

9959

AN:

15366

East Asian (EAS)

AF:

0.706

AC:

22798

AN:

32274

South Asian (SAS)

AF:

0.674

AC:

33283

AN:

49374

European-Finnish (FIN)

AF:

0.724

AC:

23339

AN:

32222

Middle Eastern (MID)

AF:

0.637

AC:

2525

AN:

3962

European-Non Finnish (NFE)

AF:

0.643

AC:

317082

AN:

493368

Other (OTH)

AF:

0.639

AC:

21878

AN:

34242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

7701

15402

23103

30804

38505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5888

11776

17664

23552

29440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.622

AC:

94446

AN:

151800

Hom.:

29675

Cov.:

AF XY:

0.626

AC XY:

46478

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.540

AC:

22340

AN:

41344

American (AMR)

AF:

0.629

AC:

9602

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.642

AC:

2226

AN:

3466

East Asian (EAS)

AF:

0.738

AC:

3812

AN:

5164

South Asian (SAS)

AF:

0.677

AC:

3252

AN:

4804

European-Finnish (FIN)

AF:

0.727

AC:

7663

AN:

10536

Middle Eastern (MID)

AF:

0.627

AC:

183

AN:

292

European-Non Finnish (NFE)

AF:

0.641

AC:

43530

AN:

67922

Other (OTH)

AF:

0.611

AC:

1289

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1802

3604

5405

7207

9009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.439

Hom.:

1426

Bravo

AF:

0.611

Asia WGS

AF:

0.692

AC:

2407

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.81

Mutation Taster

=95/5

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over