rs17369578

Variant names:

• chr16-56997899-G-A
• rs17369578
• NM_001384950.1:c.-128+8282G>A

Variant summary

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

The NM_001384950.1(NLRC5):​c.-128+8282G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,190 control chromosomes in the GnomAD database, including 262 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 0.051 (262 hom., cov: 31)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 9 publications found

Genes affected

NLRC5 (HGNC:29933): (NLR family CARD domain containing 5) This gene encodes a member of the caspase recruitment domain-containing NLR family. This gene plays a role in cytokine response and antiviral immunity through its inhibition of NF-kappa-B activation and negative regulation of type I interferon signaling pathways. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.-128+8282G>A		intron_variant	Intron 1 of 48	ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.-128+8282G>A		intron_variant	Intron 1 of 48		NM_001384950.1	ENSP00000509992.1
NLRC5	ENST00000262510.10	c.-128+8304G>A		intron_variant	Intron 1 of 48	5		ENSP00000262510.6
NLRC5	ENST00000538273.5	n.33+8304G>A		intron_variant	Intron 1 of 2	2
NLRC5	ENST00000539881.5	n.-128+8282G>A		intron_variant	Intron 1 of 24	2		ENSP00000441679.1

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7831 AN: 152072 Hom.: 261 Cov.: 31

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0451

Gnomad OTH AF: 0.0445

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

GnomAD4 genome AF: 0.0515 AC: 7833 AN: 152190 Hom.: 262 Cov.: 31 AF XY: 0.0559 AC XY: 4160 AN XY: 74404

African (AFR) AF: 0.0437 AC: 1816 AN: 41530

American (AMR) AF: 0.0302 AC: 462 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.0594 AC: 307 AN: 5170

South Asian (SAS) AF: 0.161 AC: 777 AN: 4814

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0451 AC: 3069 AN: 68008

Other (OTH) AF: 0.0440 AC: 93 AN: 2112

Alfa AF: 0.0519 Hom.: 152

Bravo AF: 0.0415

Asia WGS AF: 0.110 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-0.37
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: rs17369578; hg19: chr16-57031811;