11-7039439-A-T

Position:

• chr11-7039439-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_176822.4(NLRP14):​c.290-275A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 152,154 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.031 (141 hom., cov: 31)
• Consequence: NLRP14 NM_176822.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-7039439-A-T is Benign according to our data. Variant chr11-7039439-A-T is described in ClinVar as [Benign]. Clinvar id is 1227247.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRP14	NM_176822.4	c.290-275A>T		intron_variant		ENST00000299481.5	NP_789792.1
NLRP14	XM_011520044.2	c.290-275A>T		intron_variant			XP_011518346.1
NLRP14	XM_047426867.1	c.290-275A>T		intron_variant			XP_047282823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRP14	ENST00000299481.5	c.290-275A>T		intron_variant		5	NM_176822.4	ENSP00000299481	P1

Frequencies

GnomAD3 genomes AF: 0.0313 AC: 4752 AN: 152036 Hom.: 140 Cov.: 31

Gnomad AFR AF: 0.00826

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0328

Gnomad OTH AF: 0.0398

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0312 AC: 4752 AN: 152154 Hom.: 141 Cov.: 31 AF XY: 0.0329 AC XY: 2447 AN XY: 74354

Gnomad4 AFR AF: 0.00828

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0328

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0147 Hom.: 5

Bravo AF: 0.0263

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs76261649; hg19: chr11-7060670;