rs576491436

Variant names:

• chr11-67991711-C-T
• rs576491436
• NM_030930.4:c.1629G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_030930.4(UNC93B1):​c.1629G>A​(p.Glu543Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 1,535,762 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: UNC93B1 NM_030930.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.138
• 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)
• systemic lupus erythematosus

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 11-67991711-C-T is Benign according to our data. Variant chr11-67991711-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 537930.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.138 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00189 (288/152278) while in subpopulation AFR AF = 0.0064 (266/41570). AF 95% confidence interval is 0.00577. There are 2 homozygotes in GnomAd4. There are 136 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 SD,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.1629G>A	p.Glu543Glu	synonymous	Exon 11 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.1629G>A	p.Glu543Glu	synonymous	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.1668G>A	p.Glu556Glu	synonymous	Exon 11 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1653G>A	p.Glu551Glu	synonymous	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 288 AN: 152162 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000334 AC: 43 AN: 128812 AF XY: 0.000313

Gnomad AFR exome AF: 0.00561

Gnomad AMR exome AF: 0.000249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000163 AC: 225 AN: 1383484 Hom.: 1 Cov.: 31 AF XY: 0.000164 AC XY: 112 AN XY: 683138

African (AFR) AF: 0.00575 AC: 181 AN: 31492

American (AMR) AF: 0.000333 AC: 12 AN: 36014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25140

East Asian (EAS) AF: 0.00 AC: 0 AN: 35866

South Asian (SAS) AF: 0.0000756 AC: 6 AN: 79360

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33966

Middle Eastern (MID) AF: 0.000492 AC: 2 AN: 4064

European-Non Finnish (NFE) AF: 0.00000648 AC: 7 AN: 1079798

Other (OTH) AF: 0.000294 AC: 17 AN: 57784

GnomAD4 genome AF: 0.00189 AC: 288 AN: 152278 Hom.: 2 Cov.: 33 AF XY: 0.00183 AC XY: 136 AN XY: 74460

African (AFR) AF: 0.00640 AC: 266 AN: 41570

American (AMR) AF: 0.00105 AC: 16 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67982

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.00196

ClinVar

ClinVar submissions

Significance: Likely 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
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.7
DANN	Benign	0.92
PhyloP100		-0.14

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: rs576491436; hg19: chr11-67759182;