rs144979304

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.907-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,539,932 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

UNC93B1
NM_030930.4 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.498

Publications

1 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 (BayesDel_noAF=-0.79).

BP6

Variant 11-67996789-G-A is Benign according to our data. Variant chr11-67996789-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 537924.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 = 0.00313 (476/152300) while in subpopulation NFE AF = 0.0044 (299/68006). AF 95% confidence interval is 0.00399. There are 4 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
UNC93B1	NM_030930.4 link	c.907-5C>T	splice_region_variant, intron_variant	Intron 7 of 10	ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1 link	c.496-5C>T	splice_region_variant, intron_variant	Intron 5 of 8		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.352-5C>T	splice_region_variant, intron_variant	Intron 4 of 7		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.907-5C>T		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_030930.4	ENSP00000227471.3
UNC93B1	ENST00000533424.6 link	n.1401-5C>T		splice_region_variant, intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00364

AC:

610

AN:

167386

AF XY:

0.00342

show subpopulations

Gnomad AFR exome

AF:

0.000884

Gnomad AMR exome

AF:

0.000793

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00626

Gnomad NFE exome

AF:

0.00388

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00390

AC:

5406

AN:

1387632

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

2630

AN XY:

681588

show subpopulations

African (AFR)

AF:

0.000670

AC:

AN:

31360

American (AMR)

AF:

0.000870

AC:

AN:

36794

Ashkenazi Jewish (ASJ)

AF:

0.0208

AC:

515

AN:

24808

East Asian (EAS)

AF:

0.00

AC:

AN:

35594

South Asian (SAS)

AF:

0.000573

AC:

AN:

78468

European-Finnish (FIN)

AF:

0.00659

AC:

326

AN:

49482

Middle Eastern (MID)

AF:

0.000456

AC:

AN:

4384

European-Non Finnish (NFE)

AF:

0.00395

AC:

4221

AN:

1069724

Other (OTH)

AF:

0.00428

AC:

244

AN:

57018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

272

543

815

1086

1358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<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:

0.00313

AC:

476

AN:

152300

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41574

American (AMR)

AF:

0.00124

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00556

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00440

AC:

299

AN:

68006

Other (OTH)

AF:

0.00473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00471

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

UNC93B1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

(source)

DANN

Benign

0.81

PhyloP100

0.50

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over