11-67991615-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_030930.4(UNC93B1):c.1725C>G(p.Pro575Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,499,800 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P575P) 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 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.62

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)

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=-0.88).

BP6

Variant 11-67991615-G-C is Benign according to our data. Variant chr11-67991615-G-C is described in ClinVar as [Benign]. Clinvar id is 782776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00591 (899/152182) while in subpopulation NFE AF = 0.00917 (623/67948). 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1725C>G	p.Pro575Pro	synonymous_variant	Exon 11 of 11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.1314C>G	p.Pro438Pro	synonymous_variant	Exon 9 of 9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.1170C>G	p.Pro390Pro	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.1725C>G	p.Pro575Pro	synonymous_variant	Exon 11 of 11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 link	n.*203C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152074

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:

0.00917

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00609

AC:

582

AN:

95542

AF XY:

0.00603

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.00431

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00196

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.00919

AC:

12387

AN:

1347618

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

5924

AN XY:

664088

show subpopulations

African (AFR)

AF:

0.00127

AC:

AN:

27610

American (AMR)

AF:

0.00574

AC:

172

AN:

29972

Ashkenazi Jewish (ASJ)

AF:

0.00392

AC:

AN:

23468

East Asian (EAS)

AF:

0.0000303

AC:

AN:

33048

South Asian (SAS)

AF:

0.00173

AC:

130

AN:

74938

European-Finnish (FIN)

AF:

0.00214

AC:

AN:

33182

Middle Eastern (MID)

AF:

0.00738

AC:

AN:

3930

European-Non Finnish (NFE)

AF:

0.0107

AC:

11418

AN:

1065318

Other (OTH)

AF:

0.00782

AC:

439

AN:

56152

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

734

1468

2203

2937

3671

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00591

AC:

899

AN:

152182

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

420

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00209

AC:

AN:

41546

American (AMR)

AF:

0.00862

AC:

132

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00917

AC:

623

AN:

67948

Other (OTH)

AF:

0.0104

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

128

170

213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00649

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

UNC93B1: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

(source)

DANN

Benign

0.53

PhyloP100

-1.6

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

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11-67991615-G-C

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