rs11543208

Variant names:

• chr11-67995811-G-A
• rs11543208
• NM_030930.4:c.1163C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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. 14/20 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.75
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 470488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.1163C>T	p.Ala388Val	missense	Exon 9 of 11	NP_112192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.1163C>T	p.Ala388Val	missense	Exon 9 of 11	ENSP00000227471.3
	UNC93B1	ENST00000864508.1		c.1202C>T	p.Ala401Val	missense	Exon 9 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1187C>T	p.Ala396Val	missense	Exon 9 of 11	ENSP00000534568.1

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

GnomAD2 exomes AF: 0.0141 AC: 2054 AN: 145576 AF XY: 0.0146

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 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

African (AFR) AF: 0.00225 AC: 71 AN: 31510

American (AMR) AF: 0.00620 AC: 221 AN: 35638

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 531 AN: 25086

East Asian (EAS) AF: 0.0000840 AC: 3 AN: 35710

South Asian (SAS) AF: 0.0175 AC: 1385 AN: 79044

European-Finnish (FIN) AF: 0.0185 AC: 879 AN: 47390

Middle Eastern (MID) AF: 0.0163 AC: 66 AN: 4058

European-Non Finnish (NFE) AF: 0.0175 AC: 18823 AN: 1078258

Other (OTH) AF: 0.0140 AC: 810 AN: 57762

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

African (AFR) AF: 0.00294 AC: 122 AN: 41520

American (AMR) AF: 0.00621 AC: 95 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0253 AC: 88 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5130

South Asian (SAS) AF: 0.0156 AC: 75 AN: 4820

European-Finnish (FIN) AF: 0.0180 AC: 191 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0172 AC: 1170 AN: 67962

Other (OTH) AF: 0.0123 AC: 26 AN: 2108

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Herpes simplex encephalitis, susceptibility to, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		3.8
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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs11543208; hg19: chr11-67763282;