11-67991783-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030930.4(UNC93B1):c.1557C>G(p.Arg519Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,433,224 control chromosomes in the GnomAD database, including 45,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 6376 hom., cov: 34)

Exomes 𝑓: 0.24 ( 39511 hom. )

Consequence

UNC93B1
NM_030930.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0730

Publications

7 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-67991783-G-C is Benign according to our data. Variant chr11-67991783-G-C is described in ClinVar as Benign. ClinVar VariationId is 537932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1557C>G	p.Arg519Arg	synonymous_variant	Exon 11 of 11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.1146C>G	p.Arg382Arg	synonymous_variant	Exon 9 of 9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.1002C>G	p.Arg334Arg	synonymous_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.1557C>G	p.Arg519Arg	synonymous_variant	Exon 11 of 11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 link	n.*35C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

42262

AN:

125786

Hom.:

6375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.331

GnomAD2 exomes

AF:

0.122

AC:

14620

AN:

119604

AF XY:

0.114

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.0816

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.244

AC:

318737

AN:

1307336

Hom.:

39511

Cov.:

AF XY:

0.241

AC XY:

155403

AN XY:

645510

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.415

AC:

12508

AN:

30110

American (AMR)

AF:

0.135

AC:

4591

AN:

34048

Ashkenazi Jewish (ASJ)

AF:

0.282

AC:

6513

AN:

23130

East Asian (EAS)

AF:

0.165

AC:

5710

AN:

34562

South Asian (SAS)

AF:

0.140

AC:

10534

AN:

75464

European-Finnish (FIN)

AF:

0.183

AC:

5642

AN:

30862

Middle Eastern (MID)

AF:

0.247

AC:

947

AN:

3840

European-Non Finnish (NFE)

AF:

0.254

AC:

258785

AN:

1020702

Other (OTH)

AF:

0.247

AC:

13507

AN:

54618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

9986

19972

29958

39944

49930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8786

17572

26358

35144

43930

<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:

0.336

AC:

42303

AN:

125888

Hom.:

6376

Cov.:

AF XY:

0.328

AC XY:

19999

AN XY:

60966

show subpopulations

African (AFR)

AF:

0.448

AC:

17108

AN:

38202

American (AMR)

AF:

0.235

AC:

2945

AN:

12550

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

920

AN:

2726

East Asian (EAS)

AF:

0.200

AC:

912

AN:

4558

South Asian (SAS)

AF:

0.193

AC:

722

AN:

3738

European-Finnish (FIN)

AF:

0.216

AC:

1621

AN:

7514

Middle Eastern (MID)

AF:

0.268

AC:

AN:

272

European-Non Finnish (NFE)

AF:

0.318

AC:

17143

AN:

53882

Other (OTH)

AF:

0.330

AC:

575

AN:

1744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1594

3189

4783

6378

7972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<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:

0.262

Hom.:

906

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Feb 03, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.073

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over