11-67991561-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_030930.4(UNC93B1):​c.1779G>A​(p.Gly593Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,469,594 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 (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

UNC93B1
NM_030930.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.320
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-67991561-C-T is Benign according to our data. Variant chr11-67991561-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 537940.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00052 (79/152036) while in subpopulation AFR AF= 0.00166 (69/41514). AF 95% confidence interval is 0.00135. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNC93B1NM_030930.4 linkc.1779G>A p.Gly593Gly synonymous_variant Exon 11 of 11 ENST00000227471.7 NP_112192.2 Q9H1C4
UNC93B1XM_011545290.1 linkc.1368G>A p.Gly456Gly synonymous_variant Exon 9 of 9 XP_011543592.1
UNC93B1XM_011545291.3 linkc.1224G>A p.Gly408Gly 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.1779G>A p.Gly593Gly synonymous_variant Exon 11 of 11 1 NM_030930.4 ENSP00000227471.3 Q9H1C4

Frequencies

GnomAD3 genomes
AF:
0.000520
AC:
79
AN:
151920
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00167
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000483
AC:
4
AN:
82760
Hom.:
0
AF XY:
0.0000431
AC XY:
2
AN XY:
46452
show subpopulations
Gnomad AFR exome
AF:
0.00143
Gnomad AMR exome
AF:
0.0000633
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000643
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000660
AC:
87
AN:
1317558
Hom.:
0
Cov.:
30
AF XY:
0.0000541
AC XY:
35
AN XY:
646676
show subpopulations
Gnomad4 AFR exome
AF:
0.00179
Gnomad4 AMR exome
AF:
0.0000739
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000557
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000305
Gnomad4 OTH exome
AF:
0.0000366
GnomAD4 genome
AF:
0.000520
AC:
79
AN:
152036
Hom.:
0
Cov.:
33
AF XY:
0.000457
AC XY:
34
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00166
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000737
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000674
Hom.:
0

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
Jan 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
4.5
DANN
Benign
0.94

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2375183; hg19: chr11-67759032; API