chr16-56990405-G-C

Position:

• chr16-56990405-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384950.1(NLRC5):​c.-128+788G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 152,160 control chromosomes in the GnomAD database, including 806 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 0.097 (806 hom., cov: 32)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRC5	NM_001384950.1	c.-128+788G>C		intron_variant		ENST00000688547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRC5	ENST00000688547.1	c.-128+788G>C		intron_variant			NM_001384950.1	P2

Frequencies

GnomAD3 genomes AF: 0.0971 AC: 14759 AN: 152042 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0784

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0943

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

GnomAD4 genome AF: 0.0970 AC: 14767 AN: 152160 Hom.: 806 Cov.: 32 AF XY: 0.0927 AC XY: 6893 AN XY: 74390

Gnomad4 AFR AF: 0.0938

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0214

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.103 Hom.: 102

Bravo AF: 0.0975

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs17290922; hg19: chr16-57024317;