17-5499637-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001162371.3(LOC728392):​c.*880T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 381,492 control chromosomes in the GnomAD database, including 59,146 homozygotes. 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 0.61 (31241 hom., cov: 31)
  • Exomes 𝑓: 0.49 (27905 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93285 AN: 151812 Hom.: 31192 Cov.: 31

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.486 AC: 111495 AN: 229562 Hom.: 27905 Cov.: 5 AF XY: 0.486 AC XY: 52994 AN XY: 108980

African (AFR) AF: 0.893 AC: 3976 AN: 4450

American (AMR) AF: 0.507 AC: 144 AN: 284

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 758 AN: 1434

East Asian (EAS) AF: 0.968 AC: 983 AN: 1016

South Asian (SAS) AF: 0.655 AC: 3137 AN: 4788

European-Finnish (FIN) AF: 0.597 AC: 43 AN: 72

Middle Eastern (MID) AF: 0.606 AC: 292 AN: 482

European-Non Finnish (NFE) AF: 0.468 AC: 98052 AN: 209386

Other (OTH) AF: 0.537 AC: 4110 AN: 7650

GnomAD4 genome AF: 0.615 AC: 93386 AN: 151930 Hom.: 31241 Cov.: 31 AF XY: 0.622 AC XY: 46178 AN XY: 74240

African (AFR) AF: 0.850 AC: 35215 AN: 41434

American (AMR) AF: 0.498 AC: 7612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3468

East Asian (EAS) AF: 0.973 AC: 5022 AN: 5160

South Asian (SAS) AF: 0.663 AC: 3198 AN: 4820

European-Finnish (FIN) AF: 0.646 AC: 6805 AN: 10540

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31949 AN: 67926

Other (OTH) AF: 0.583 AC: 1229 AN: 2108

Alfa AF: 0.498 Hom.: 32261

Bravo AF: 0.614

Asia WGS AF: 0.832 AC: 2892 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.6
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;