rs2375182

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1768G>T(p.Gly590Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,488,914 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G590R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0089 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 27 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.38

Publications

2 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)

UNC93B1 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=0.0035933256).

BP6

Variant 11-67991572-C-A is Benign according to our data. Variant chr11-67991572-C-A is described in ClinVar as [Benign]. Clinvar id is 470495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00888 (1351/152056) while in subpopulation AFR AF = 0.0232 (962/41536). AF 95% confidence interval is 0.0219. There are 12 homozygotes in GnomAd4. There are 652 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1768G>T	p.Gly590Trp	missense_variant	Exon 11 of 11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.1357G>T	p.Gly453Trp	missense_variant	Exon 9 of 9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.1213G>T	p.Gly405Trp	missense_variant	Exon 8 of 8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.1768G>T	p.Gly590Trp	missense_variant	Exon 11 of 11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 link	n.*246G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00887

AC:

1347

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.00767

GnomAD2 exomes

AF:

0.00290

AC:

269

AN:

92742

AF XY:

0.00255

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00266

Gnomad EAS exome

AF:

0.000505

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00399

AC:

5336

AN:

1336858

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2557

AN XY:

658162

show subpopulations

African (AFR)

AF:

0.0265

AC:

717

AN:

27008

American (AMR)

AF:

0.00370

AC:

109

AN:

29422

Ashkenazi Jewish (ASJ)

AF:

0.00316

AC:

AN:

23128

East Asian (EAS)

AF:

0.000345

AC:

AN:

31844

South Asian (SAS)

AF:

0.000230

AC:

AN:

74010

European-Finnish (FIN)

AF:

0.000332

AC:

AN:

33142

Middle Eastern (MID)

AF:

0.00179

AC:

AN:

3918

European-Non Finnish (NFE)

AF:

0.00382

AC:

4044

AN:

1058824

Other (OTH)

AF:

0.00625

AC:

347

AN:

55562

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

316

632

948

1264

1580

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00888

AC:

1351

AN:

152056

Hom.:

Cov.:

AF XY:

0.00877

AC XY:

652

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0232

AC:

962

AN:

41536

American (AMR)

AF:

0.00484

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.000389

AC:

AN:

5136

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00426

AC:

289

AN:

67876

Other (OTH)

AF:

0.00759

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

121

181

242

302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.0102

ExAC

AF:

0.00124

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

3.4

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.35

MutPred

0.47

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.043

MPC

1.3

ClinPred

0.027

GERP RS

4.6

Varity_R

0.18

gMVP

0.38

Mutation Taster

=96/4

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs2375182

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over