16-57003991-T-C

Variant names:

• chr16-57003991-T-C
• rs289707
• NM_001384950.1:c.-127-13083T>C

Variant summary

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

The NM_001384950.1(NLRC5):​c.-127-13083T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,094 control chromosomes in the GnomAD database, including 39,152 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 0.71 (39110 hom., cov: 30)
  • Exomes 𝑓: 0.84 (42 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.21
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.-127-13083T>C		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.-127-13083T>C		intron_variant	Intron 1 of 48		NM_001384950.1	ENSP00000509992.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107729 AN: 151860 Hom.: 39075 Cov.: 30

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.737

GnomAD4 exome AF: 0.836 AC: 97 AN: 116 Hom.: 42 Cov.: 0 AF XY: 0.845 AC XY: 71 AN XY: 84

African (AFR) AF: 0.667 AC: 4 AN: 6

American (AMR) AF: 0.750 AC: 3 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.643 AC: 9 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.900 AC: 72 AN: 80

Other (OTH) AF: 0.800 AC: 8 AN: 10

GnomAD4 genome AF: 0.709 AC: 107813 AN: 151978 Hom.: 39110 Cov.: 30 AF XY: 0.702 AC XY: 52157 AN XY: 74264

African (AFR) AF: 0.557 AC: 23075 AN: 41402

American (AMR) AF: 0.719 AC: 10973 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2948 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3345 AN: 5150

South Asian (SAS) AF: 0.583 AC: 2802 AN: 4804

European-Finnish (FIN) AF: 0.740 AC: 7819 AN: 10566

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54290 AN: 68008

Other (OTH) AF: 0.735 AC: 1550 AN: 2108

Alfa AF: 0.768 Hom.: 172681

Bravo AF: 0.706

Asia WGS AF: 0.594 AC: 2065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.41
PhyloP100		-3.2
PromoterAI		-0.0073	Neutral
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: rs289707; hg19: chr16-57037903;