11-67991616-G-T

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.1724C>A(p.Pro575His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 1,501,360 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P575Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 68 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.49

Publications

0 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:

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=0.0065273046).

BP6

Variant 11-67991616-G-T is Benign according to our data. Variant chr11-67991616-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 782777.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00591 (899/152222) while in subpopulation NFE AF = 0.00917 (623/67966). AF 95% confidence interval is 0.00857. There are 6 homozygotes in GnomAd4. There are 420 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 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.1724C>A	p.Pro575His	missense	Exon 11 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.1724C>A	p.Pro575His	missense	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
UNC93B1	ENST00000864508.1		c.1763C>A	p.Pro588His	missense	Exon 11 of 11	ENSP00000534567.1
UNC93B1	ENST00000864509.1		c.1748C>A	p.Pro583His	missense	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00595

AC:

577

AN:

96914

AF XY:

0.00591

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00571

Gnomad ASJ exome

AF:

0.00409

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00216

Gnomad NFE exome

AF:

0.00980

Gnomad OTH exome

AF:

0.00984

GnomAD4 exome

AF:

0.00918

AC:

12381

AN:

1349138

Hom.:

Cov.:

AF XY:

0.00891

AC XY:

5922

AN XY:

664906

show subpopulations

African (AFR)

AF:

0.00126

AC:

AN:

27678

American (AMR)

AF:

0.00568

AC:

172

AN:

30282

Ashkenazi Jewish (ASJ)

AF:

0.00391

AC:

AN:

23548

East Asian (EAS)

AF:

0.00

AC:

AN:

33150

South Asian (SAS)

AF:

0.00173

AC:

130

AN:

75186

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

33204

Middle Eastern (MID)

AF:

0.00736

AC:

AN:

3942

European-Non Finnish (NFE)

AF:

0.0107

AC:

11413

AN:

1065926

Other (OTH)

AF:

0.00779

AC:

438

AN:

56222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

727

1454

2182

2909

3636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

456

912

1368

1824

2280

<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:

0.00591

AC:

899

AN:

152222

Hom.:

Cov.:

AF XY:

0.00564

AC XY:

420

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41552

American (AMR)

AF:

0.00862

AC:

132

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00145

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00917

AC:

623

AN:

67966

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00298

Hom.:

Bravo

AF:

0.00650

ExAC

AF:

0.00195

AC:

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

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

PhyloP100

1.5

PrimateAI

Pathogenic

0.79

REVEL

Benign

0.022

Sift4G

Uncertain

0.0080

Polyphen

0.70

Vest4

0.20

MVP

0.043

MPC

0.91

ClinPred

0.0090

GERP RS

2.4

Varity_R

0.040

gMVP

0.40

Mutation Taster

=100/0

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.

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