16-56990750-T-C

Variant names:

• chr16-56990750-T-C
• rs1566439
• NM_001384950.1:c.-128+1133T>C

Variant summary

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

The NM_032206.5(NLRC5):​c.-128+1155T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,000 control chromosomes in the GnomAD database, including 11,361 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 0.37 (11360 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: NLRC5 NM_032206.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 30 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032206.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC5	NM_001384950.1	MANE Select	c.-128+1133T>C		intron	N/A	NP_001371879.1
	NLRC5	NM_032206.5		c.-128+1155T>C		intron	N/A	NP_115582.4
	NLRC5	NM_001384952.1		c.-128+1155T>C		intron	N/A	NP_001371881.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NLRC5	ENST00000688547.1	MANE Select	c.-128+1133T>C		intron	N/A	ENSP00000509992.1
	NLRC5	ENST00000262510.10	TSL:5	c.-128+1155T>C		intron	N/A	ENSP00000262510.6
	NLRC5	ENST00000877315.1		c.-128+1155T>C		intron	N/A	ENSP00000547374.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56331 AN: 151874 Hom.: 11355 Cov.: 31

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.371 AC: 56365 AN: 151992 Hom.: 11360 Cov.: 31 AF XY: 0.378 AC XY: 28038 AN XY: 74270

African (AFR) AF: 0.215 AC: 8906 AN: 41478

American (AMR) AF: 0.483 AC: 7375 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3086 AN: 5160

South Asian (SAS) AF: 0.397 AC: 1915 AN: 4818

European-Finnish (FIN) AF: 0.472 AC: 4969 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27282 AN: 67952

Other (OTH) AF: 0.404 AC: 854 AN: 2112

Alfa AF: 0.395 Hom.: 30437

Bravo AF: 0.366

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.58
DANN	Benign	0.66
PhyloP100		-1.5
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: rs1566439; hg19: chr16-57024662;