rs11543208

chr11-67995811-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030930.4(UNC93B1):c.1163C>T(p.Ala388Val) variant causes a missense change. The variant allele was found at a frequency of 0.0159 in 1,546,586 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (20 hom., cov: 29)
  • Exomes 𝑓: 0.016 (186 hom.)
• Consequence: UNC93B1 NM_030930.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.75

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004144609).
• BP6: Variant 11-67995811-G-A is Benign according to our data. Variant chr11-67995811-G-A is described in ClinVar as [Benign]. Clinvar id is 470488.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1781/152130) while in subpopulation NFE AF= 0.0172 (1170/67962). AF 95% confidence interval is 0.0164. There are 20 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC93B1	NM_030930.4	c.1163C>T	p.Ala388Val	missense_variant	9/11	ENST00000227471.7
UNC93B1	XM_011545290.1	c.752C>T	p.Ala251Val	missense_variant	7/9
UNC93B1	XM_011545291.3	c.608C>T	p.Ala203Val	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1163C>T	p.Ala388Val	missense_variant	9/11	1	NM_030930.4	P1
UNC93B1	ENST00000525368.1	n.170C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1783 AN: 152012 Hom.: 21 Cov.: 29

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.0253

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0125

GnomAD3 exomes AF: 0.0141 AC: 2054 AN: 145576 Hom.: 23 AF XY: 0.0146 AC XY: 1146 AN XY: 78434

Gnomad AFR exome AF: 0.00256

Gnomad AMR exome AF: 0.00568

Gnomad ASJ exome AF: 0.0196

Gnomad EAS exome AF: 0.0000948

Gnomad SAS exome AF: 0.0163

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0193

Gnomad OTH exome AF: 0.0162

GnomAD4 exome AF: 0.0163 AC: 22789 AN: 1394456 Hom.: 186 Cov.: 36 AF XY: 0.0166 AC XY: 11403 AN XY: 687776

Gnomad4 AFR exome AF: 0.00225

Gnomad4 AMR exome AF: 0.00620

Gnomad4 ASJ exome AF: 0.0212

Gnomad4 EAS exome AF: 0.0000840

Gnomad4 SAS exome AF: 0.0175

Gnomad4 FIN exome AF: 0.0185

Gnomad4 NFE exome AF: 0.0175

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0117 AC: 1781 AN: 152130 Hom.: 20 Cov.: 29 AF XY: 0.0116 AC XY: 865 AN XY: 74362

Gnomad4 AFR AF: 0.00294

Gnomad4 AMR AF: 0.00621

Gnomad4 ASJ AF: 0.0253

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0179 Hom.: 4

Bravo AF: 0.0105

TwinsUK AF: 0.0140 AC: 52

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.00302 AC: 10

ESP6500EA AF: 0.0114 AC: 81

ExAC AF: 0.00654 AC: 542

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	12
Dann	Benign	0.84
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.23
Sift	Benign	0.047	D
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.16
MPC		0.42
ClinPred		0.0039	T
GERP RS		2.9
Varity_R		0.016
gMVP		0.15

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: rs11543208; hg19: chr11-67763282;