Genetic Variant LOC728392:c.*880T>A (chr17-5499637-A-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001162371.3(LOC728392):c.*880T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LOC728392
NM_001162371.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.536

Publications

27 publications found

Variant links:

Genes affected

LOC728392 (HGNC:0):

LOC728392 links:

NLRP1 (HGNC:14374): (NLR family pyrin domain containing 1) This gene encodes a member of the Ced-4 family of apoptosis proteins. Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The encoded protein contains a distinct N-terminal pyrin-like motif, which is possibly involved in protein-protein interactions. This protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to induce apoptosis in cells. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]

NLRP1 Gene-Disease associations (from GenCC):

corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome
Inheritance: AD, SD Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
autoinflammation with arthritis and dyskeratosis
Inheritance: AR, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

NLRP1 links:

LOC124900388 (HGNC:):

LOC124900388 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC728392	NM_001162371.3 link	c.*880T>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000568641.2	NP_001155843.1
LOC124900388	XM_047437232.1 link	c.*166T>A		3_prime_UTR_variant	Exon 2 of 2		XP_047293188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286190	ENST00000568641.2 link	c.*880T>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001162371.3	ENSP00000499042.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151886

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

230516

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

109408

African (AFR)

AF:

0.00

AC:

AN:

4460

American (AMR)

AF:

0.00

AC:

AN:

288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1436

East Asian (EAS)

AF:

0.00

AC:

AN:

1018

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

484

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

210264

Other (OTH)

AF:

0.00

AC:

AN:

7682

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74160

African (AFR)

AF:

0.00

AC:

AN:

41324

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.0

(source)

DANN

Benign

0.17

PhyloP100

-0.54

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over