11-67991615-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_030930.4(UNC93B1):c.1725C>G(p.Pro575=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62

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 -17 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. Variant chr11-67991615-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC93B1	NM_030930.4	c.1725C>G	p.Pro575=	synonymous_variant	11/11	ENST00000227471.7
UNC93B1	XM_011545290.1	c.1314C>G	p.Pro438=	synonymous_variant	9/9
UNC93B1	XM_011545291.3	c.1170C>G	p.Pro390=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1725C>G	p.Pro575=	synonymous_variant	11/11	1	NM_030930.4	P1

Frequencies

GnomAD3 genomes AF: 0.00592 AC: 900 AN: 152074 Hom.: 6 Cov.: 33

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

GnomAD3 exomes AF: 0.00609 AC: 582 AN: 95542 Hom.: 3 AF XY: 0.00603 AC XY: 323 AN XY: 53596

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 SAS exome AF: 0.00185

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.: 68 Cov.: 30 AF XY: 0.00892 AC XY: 5924 AN XY: 664088

Gnomad4 AFR exome AF: 0.00127

Gnomad4 AMR exome AF: 0.00574

Gnomad4 ASJ exome AF: 0.00392

Gnomad4 EAS exome AF: 0.0000303

Gnomad4 SAS exome AF: 0.00173

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00782

GnomAD4 genome AF: 0.00591 AC: 899 AN: 152182 Hom.: 6 Cov.: 33 AF XY: 0.00565 AC XY: 420 AN XY: 74396

Gnomad4 AFR AF: 0.00209

Gnomad4 AMR AF: 0.00862

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00917

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00298 Hom.: 4

Bravo AF: 0.00649

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

UNC93B1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.11
Dann	Benign	0.53

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: rs568350079; hg19: chr11-67759086;