rs146593182

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030930.4(UNC93B1):c.385C>A(p.Leu129Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,611,194 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 23 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.87

Publications

4 publications found

Variant links:

Genes affected

UNC93B1 (HGNC:13481): (unc-93 homolog B1, TLR signaling regulator) This gene encodes a protein that is involved in innate and adaptive immune response by regulating toll-like receptor signaling. The encoded protein traffics nucleotide sensing toll-like receptors to the endolysosome from the endoplasmic reticulum. Deficiency of the encoded protein has been associated with herpes simplex encephalitis. [provided by RefSeq, Feb 2014]

UNC93B1 Gene-Disease associations (from GenCC):

herpes simplex encephalitis, susceptibility to, 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
systemic lupus erythematosus
Inheritance: SD Classification: MODERATE Submitted by: ClinGen

UNC93B1 links:

ENSG00000309414 (HGNC:):

ENSG00000309414 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008801967).

BP6

Variant 11-68003029-G-T is Benign according to our data. Variant chr11-68003029-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 470497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00284 (432/152116) while in subpopulation AMR AF = 0.00687 (105/15288). AF 95% confidence interval is 0.0058. There are 1 homozygotes in GnomAd4. There are 228 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.385C>A	p.Leu129Ile	missense	Exon 3 of 11	NP_112192.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.385C>A	p.Leu129Ile	missense	Exon 3 of 11	ENSP00000227471.3	Q9H1C4
UNC93B1	ENST00000864508.1		c.424C>A	p.Leu142Ile	missense	Exon 3 of 11	ENSP00000534567.1
UNC93B1	ENST00000864509.1		c.385C>A	p.Leu129Ile	missense	Exon 3 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

431

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00688

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00500

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.00863

GnomAD2 exomes

AF:

0.00381

AC:

928

AN:

243836

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.000535

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00334

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.00289

AC:

4224

AN:

1459078

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

2252

AN XY:

725626

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

33418

American (AMR)

AF:

0.00605

AC:

269

AN:

44432

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

351

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39582

South Asian (SAS)

AF:

0.00568

AC:

487

AN:

85718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52910

Middle Eastern (MID)

AF:

0.0374

AC:

215

AN:

5746

European-Non Finnish (NFE)

AF:

0.00231

AC:

2571

AN:

1110902

Other (OTH)

AF:

0.00463

AC:

279

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

233

466

700

933

1166

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:

0.00284

AC:

432

AN:

152116

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

228

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41504

American (AMR)

AF:

0.00687

AC:

105

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00500

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00307

AC:

209

AN:

67972

Other (OTH)

AF:

0.00854

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00282

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000232

AC:

ESP6500EA

AF:

0.00306

AC:

ExAC

AF:

0.00359

AC:

435

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Herpes simplex encephalitis, susceptibility to, 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0088

MetaSVM

Benign

-0.95

PhyloP100

7.9

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.92

REVEL

Benign

0.12

Sift

Benign

0.27

Sift4G

Benign

0.16

Polyphen

1.0

Vest4

0.60

MVP

0.068

MPC

1.0

ClinPred

0.023

GERP RS

4.2

Varity_R

0.24

gMVP

0.39

Mutation Taster

=79/21

polymorphism

(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