rs16965039

Variant names:

• chr16-57013387-T-C
• rs16965039
• NM_001384950.1:c.-127-3687T>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.-127-3687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 630,272 control chromosomes in the GnomAD database, including 1,151 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 0.055 (258 hom., cov: 34)
  • Exomes 𝑓: 0.057 (893 hom.)
• Consequence: NLRC5 NM_001384950.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24
• Publications: 16 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]

CFAP69P1 (HGNC:50809): (CFAP69 pseudogene 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.-127-3687T>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.-127-3687T>C		intron_variant	Intron 1 of 48		NM_001384950.1	ENSP00000509992.1

Frequencies

GnomAD3 genomes AF: 0.0554 AC: 8426 AN: 152180 Hom.: 254 Cov.: 34

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0545

Gnomad OTH AF: 0.0526

GnomAD4 exome AF: 0.0571 AC: 27275 AN: 477974 Hom.: 893 Cov.: 0 AF XY: 0.0583 AC XY: 15036 AN XY: 258002

African (AFR) AF: 0.0622 AC: 804 AN: 12924

American (AMR) AF: 0.0267 AC: 564 AN: 21092

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 772 AN: 15060

East Asian (EAS) AF: 0.0358 AC: 1121 AN: 31356

South Asian (SAS) AF: 0.0887 AC: 4695 AN: 52920

European-Finnish (FIN) AF: 0.0697 AC: 3071 AN: 44070

Middle Eastern (MID) AF: 0.0525 AC: 116 AN: 2210

European-Non Finnish (NFE) AF: 0.0541 AC: 14756 AN: 272582

Other (OTH) AF: 0.0534 AC: 1376 AN: 25760

GnomAD4 genome AF: 0.0554 AC: 8444 AN: 152298 Hom.: 258 Cov.: 34 AF XY: 0.0556 AC XY: 4141 AN XY: 74472

African (AFR) AF: 0.0614 AC: 2552 AN: 41566

American (AMR) AF: 0.0334 AC: 511 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3472

East Asian (EAS) AF: 0.0326 AC: 169 AN: 5186

South Asian (SAS) AF: 0.0925 AC: 447 AN: 4830

European-Finnish (FIN) AF: 0.0681 AC: 722 AN: 10604

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0546 AC: 3711 AN: 68026

Other (OTH) AF: 0.0535 AC: 113 AN: 2112

Alfa AF: 0.0549 Hom.: 463

Bravo AF: 0.0515

Asia WGS AF: 0.0590 AC: 207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.6
DANN	Benign	0.85
PhyloP100		3.2
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: rs16965039; hg19: chr16-57047299;