chr11-67991615-G-A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_030930.4(UNC93B1):​c.1725C>T​(p.Pro575Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 1,499,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P575P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

UNC93B1
NM_030930.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

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)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 11-67991615-G-A is Benign according to our data. Variant chr11-67991615-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1603766.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.62 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC93B1NM_030930.4 linkc.1725C>T p.Pro575Pro synonymous_variant Exon 11 of 11 ENST00000227471.7 NP_112192.2 Q9H1C4
UNC93B1XM_011545290.1 linkc.1314C>T p.Pro438Pro synonymous_variant Exon 9 of 9 XP_011543592.1
UNC93B1XM_011545291.3 linkc.1170C>T p.Pro390Pro synonymous_variant Exon 8 of 8 XP_011543593.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNC93B1ENST00000227471.7 linkc.1725C>T p.Pro575Pro synonymous_variant Exon 11 of 11 1 NM_030930.4 ENSP00000227471.3 Q9H1C4
UNC93B1ENST00000525368.1 linkn.*203C>T downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152074
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.000479
GnomAD4 exome
AF:
0.00000445
AC:
6
AN:
1347626
Hom.:
0
Cov.:
30
AF XY:
0.00000151
AC XY:
1
AN XY:
664090
show subpopulations
African (AFR)
AF:
0.000145
AC:
4
AN:
27610
American (AMR)
AF:
0.00
AC:
0
AN:
29976
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33048
South Asian (SAS)
AF:
0.00
AC:
0
AN:
74938
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33182
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3930
European-Non Finnish (NFE)
AF:
9.39e-7
AC:
1
AN:
1065322
Other (OTH)
AF:
0.0000178
AC:
1
AN:
56152
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00000658
AC:
1
AN:
152074
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74278
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41428
American (AMR)
AF:
0.00
AC:
0
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5166
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10620
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67958
Other (OTH)
AF:
0.000479
AC:
1
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
4
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1
Nov 18, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely 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
-0.84
CADD
Benign
0.15
DANN
Benign
0.87
PhyloP100
-1.6

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

Other links and lift over

dbSNP: rs568350079; hg19: chr11-67759086; API