rs117183629

Variant names:

• chr11-67999690-G-A
• rs117183629
• NM_030930.4:c.393-10C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030930.4(UNC93B1):​c.393-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,609,246 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (16 hom.)
• Consequence: UNC93B1 NM_030930.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.381

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-67999690-G-A is Benign according to our data. Variant chr11-67999690-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 403595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67999690-G-A is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00304 (463/152388) while in subpopulation NFE AF= 0.00519 (353/68036). AF 95% confidence interval is 0.00474. There are 0 homozygotes in gnomad4. There are 211 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.393-10C>T		intron_variant	Intron 3 of 10	ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1	c.-18-11C>T		intron_variant	Intron 1 of 8		XP_011543592.1
UNC93B1	XM_011545291.3	c.-243C>T		upstream_gene_variant			XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.393-10C>T		intron_variant	Intron 3 of 10	1	NM_030930.4	ENSP00000227471.3

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 463 AN: 152270 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00318 AC: 760 AN: 239324 Hom.: 3 AF XY: 0.00333 AC XY: 433 AN XY: 130172

Gnomad AFR exome AF: 0.000422

Gnomad AMR exome AF: 0.000944

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00164

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00550

Gnomad OTH exome AF: 0.00240

GnomAD4 exome AF: 0.00401 AC: 5838 AN: 1456858 Hom.: 16 Cov.: 32 AF XY: 0.00398 AC XY: 2882 AN XY: 724228

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.000992

Gnomad4 ASJ exome AF: 0.00308

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.00191

Gnomad4 NFE exome AF: 0.00477

Gnomad4 OTH exome AF: 0.00251

GnomAD4 genome AF: 0.00304 AC: 463 AN: 152388 Hom.: 0 Cov.: 33 AF XY: 0.00283 AC XY: 211 AN XY: 74530

Gnomad4 AFR AF: 0.000986

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.00519

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00459 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:3

Jun 02, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: No change to splice consensus -

not provided Other:1

-

GenomeConnect, ClinGen

Significance: not provided

Review Status: no classification provided

Collection Method: phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.39

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

Other links and lift over

dbSNP: rs117183629; hg19: chr11-67767160;