chr17-5499637-A-C

Variant names:

• chr17-5499637-A-C
• rs5862
• NM_001162371.3:c.*880T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001162371.3(LOC728392):​c.*880T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LOC728392 NM_001162371.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 27 publications found

Genes affected

LOC728392 (HGNC:0):

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

LOC124900388 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC728392	NM_001162371.3	c.*880T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000568641.2	NP_001155843.1
LOC124900388	XM_047437232.1	c.*166T>G		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	c.*880T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001162371.3	ENSP00000499042.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 230518 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 109408

African (AFR) AF: 0.00 AC: 0 AN: 4460

American (AMR) AF: 0.00 AC: 0 AN: 288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1436

East Asian (EAS) AF: 0.00 AC: 0 AN: 1018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 72

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 210266

Other (OTH) AF: 0.00 AC: 0 AN: 7682

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.1
DANN	Benign	0.19
PhyloP100		-0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5862; hg19: chr17-5402957;