dbSNP rs16965039: NLRC5:c.-127-3687T>C (chr16-57013387-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.24

Publications

16 publications found

Variant links:

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]

NLRC5 links:

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

CFAP69P1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384950.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLRC5	NM_001384950.1	MANE Select	c.-127-3687T>C	intron	N/A	NP_001371879.1	Q86WI3-1
NLRC5	NM_032206.5		c.-127-3687T>C	intron	N/A	NP_115582.4
NLRC5	NM_001384952.1		c.-127-3687T>C	intron	N/A	NP_001371881.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NLRC5	ENST00000688547.1	MANE Select	c.-127-3687T>C	intron	N/A	ENSP00000509992.1	Q86WI3-1
NLRC5	ENST00000262510.10	TSL:5	c.-127-3687T>C	intron	N/A	ENSP00000262510.6	Q86WI3-1
NLRC5	ENST00000877315.1		c.-127-3687T>C	intron	N/A	ENSP00000547374.1

Frequencies

GnomAD3 genomes

AF:

0.0554

AC:

8426

AN:

152180

Hom.:

254

Cov.:

show subpopulations

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.:

AF XY:

0.0583

AC XY:

15036

AN XY:

258002

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1221

2442

3664

4885

6106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0554

AC:

8444

AN:

152298

Hom.:

258

Cov.:

AF XY:

0.0556

AC XY:

4141

AN XY:

74472

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0546

AC:

3711

AN:

68026

Other (OTH)

AF:

0.0535

AC:

113

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

399

799

1198

1598

1997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.6

(source)

DANN

Benign

0.85

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over