rs182093266

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030930.4(UNC93B1):c.239-6C>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 0.00234 in 1,609,584 control chromosomes in the GnomAD database, including 5 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 0.0018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 5 hom. )

Consequence

UNC93B1
NM_030930.4 splice_region, intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.236

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-68003181-G-A is Benign according to our data. Variant chr11-68003181-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 537939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-68003181-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00176 (268/152134) while in subpopulation NFE AF= 0.00284 (193/67960). AF 95% confidence interval is 0.00251. There are 0 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.239-6C>T		splice_region_variant, intron_variant	Intron 2 of 10	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.-180C>T		upstream_gene_variant			XP_011543592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.239-6C>T		splice_region_variant, intron_variant	Intron 2 of 10	1	NM_030930.4	ENSP00000227471.3		Q9H1C4

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00176

AC:

431

AN:

244594

Hom.:

AF XY:

0.00166

AC XY:

221

AN XY:

133198

show subpopulations

Gnomad AFR exome

AF:

0.000521

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00320

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.00264

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00240

AC:

3496

AN:

1457450

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1636

AN XY:

725104

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00379

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000878

Gnomad4 NFE exome

AF:

0.00278

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00176

AC:

268

AN:

152134

Hom.:

Cov.:

AF XY:

0.00186

AC XY:

138

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00284

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00193

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UNC93B1: BP4 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.7

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over