chr11-67991568-C-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.1772G>A(p.Gly591Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,479,084 control chromosomes in the GnomAD database, including 7 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 Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G591G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0034 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 4 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.177

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=0.0051382184).

BP6

Variant 11-67991568-C-T is Benign according to our data. Variant chr11-67991568-C-T is described in ClinVar as Benign. ClinVar VariationId is 779710.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 = 0.00345 (525/152204) while in subpopulation AFR AF = 0.012 (497/41540). AF 95% confidence interval is 0.0111. There are 3 homozygotes in GnomAd4. There are 250 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 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.1772G>A	p.Gly591Glu	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.1772G>A	p.Gly591Glu	missense	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
UNC93B1	ENST00000864508.1		c.1811G>A	p.Gly604Glu	missense	Exon 11 of 11	ENSP00000534567.1
UNC93B1	ENST00000864509.1		c.1796G>A	p.Gly599Glu	missense	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

523

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000366

AC:

AN:

87416

AF XY:

0.000306

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.000542

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000288

Gnomad OTH exome

AF:

0.000372

GnomAD4 exome

AF:

0.000310

AC:

411

AN:

1326880

Hom.:

Cov.:

AF XY:

0.000290

AC XY:

189

AN XY:

652162

show subpopulations

African (AFR)

AF:

0.0134

AC:

355

AN:

26558

American (AMR)

AF:

0.000639

AC:

AN:

28168

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22802

East Asian (EAS)

AF:

0.00

AC:

AN:

31158

South Asian (SAS)

AF:

0.0000137

AC:

AN:

72996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33012

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3888

European-Non Finnish (NFE)

AF:

0.00000285

AC:

AN:

1053190

Other (OTH)

AF:

0.000617

AC:

AN:

55108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00345

AC:

525

AN:

152204

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0120

AC:

497

AN:

41540

American (AMR)

AF:

0.00144

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67964

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

111

139

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:

0.000185

Hom.:

Bravo

AF:

0.00393

ExAC

AF:

0.000249

AC:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Herpes simplex encephalitis, susceptibility to, 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

0.18

PrimateAI

Pathogenic

0.81

REVEL

Benign

0.029

Sift4G

Benign

0.35

Polyphen

0.011

Vest4

0.065

MVP

0.043

MPC

1.5

ClinPred

0.017

GERP RS

3.5

Varity_R

0.12

gMVP

0.24

Mutation Taster

=98/2

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