rs17279697

Variant names:

• chr11-7038518-T-A
• rs17279697
• NM_176822.4:c.-21-48T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-7038518-T-A
• chr11-7038518-T-C
• chr11-7038518-T-G

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.-21-48T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0996 in 1,400,498 control chromosomes in the GnomAD database, including 7,661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (787 hom., cov: 32)
  • Exomes 𝑓: 0.10 (6874 hom.)
• Consequence: NLRP14 NM_176822.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.450
• Publications: 3 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 (BayesDel_noAF=-0.85).
• BP6: Variant 11-7038518-T-A is Benign according to our data. Variant chr11-7038518-T-A is described in ClinVar as Benign. ClinVar VariationId is 1231883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 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.-21-48T>A		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.-21-48T>A		intron	N/A	ENSP00000299481.5	Q86W24
	NLRP14	ENST00000892206.1		c.-21-48T>A		intron	N/A	ENSP00000562265.1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15023 AN: 152174 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.0888

GnomAD4 exome AF: 0.0997 AC: 124418 AN: 1248206 Hom.: 6874 Cov.: 17 AF XY: 0.0988 AC XY: 62367 AN XY: 631410

African (AFR) AF: 0.0624 AC: 1807 AN: 28952

American (AMR) AF: 0.209 AC: 9098 AN: 43484

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 1761 AN: 24716

East Asian (EAS) AF: 0.147 AC: 5687 AN: 38708

South Asian (SAS) AF: 0.0954 AC: 7688 AN: 80620

European-Finnish (FIN) AF: 0.113 AC: 6008 AN: 53218

Middle Eastern (MID) AF: 0.0843 AC: 316 AN: 3750

European-Non Finnish (NFE) AF: 0.0942 AC: 86843 AN: 921680

Other (OTH) AF: 0.0982 AC: 5210 AN: 53078

GnomAD4 genome AF: 0.0986 AC: 15019 AN: 152292 Hom.: 787 Cov.: 32 AF XY: 0.102 AC XY: 7610 AN XY: 74462

African (AFR) AF: 0.0732 AC: 3043 AN: 41570

American (AMR) AF: 0.161 AC: 2468 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.119 AC: 617 AN: 5182

South Asian (SAS) AF: 0.106 AC: 512 AN: 4830

European-Finnish (FIN) AF: 0.119 AC: 1263 AN: 10606

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0959 AC: 6523 AN: 68018

Other (OTH) AF: 0.0879 AC: 186 AN: 2116

Alfa AF: 0.0969 Hom.: 107

Bravo AF: 0.0991

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.54
PhyloP100		-0.45
Mutation Taster		=100/0	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: rs17279697; hg19: chr11-7059749; COSMIC: COSV55072231;