chr11-67999690-G-A

Variant names:

• chr11-67999690-G-A
• rs117183629
• NM_030930.4:c.393-10C>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.393-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,609,246 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (16 hom.)
• Consequence: UNC93B1 NM_030930.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: -0.381
• Publications: 0 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-67999690-G-A is Benign according to our data. Variant chr11-67999690-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403595.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 = 0.00304 (463/152388) while in subpopulation NFE AF = 0.00519 (353/68036). AF 95% confidence interval is 0.00474. There are 0 homozygotes in GnomAd4. There are 211 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 16 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.393-10C>T		intron	N/A	NP_112192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.393-10C>T		intron	N/A	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.432-10C>T		intron	N/A	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.393-10C>T		intron	N/A	ENSP00000534568.1

Frequencies

GnomAD3 genomes AF: 0.00304 AC: 463 AN: 152270 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00519

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00318 AC: 760 AN: 239324 AF XY: 0.00333

Gnomad AFR exome AF: 0.000422

Gnomad AMR exome AF: 0.000944

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00550

Gnomad OTH exome AF: 0.00240

GnomAD4 exome AF: 0.00401 AC: 5838 AN: 1456858 Hom.: 16 Cov.: 32 AF XY: 0.00398 AC XY: 2882 AN XY: 724228

African (AFR) AF: 0.000300 AC: 10 AN: 33326

American (AMR) AF: 0.000992 AC: 44 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00308 AC: 80 AN: 26014

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39472

South Asian (SAS) AF: 0.00178 AC: 152 AN: 85228

European-Finnish (FIN) AF: 0.00191 AC: 100 AN: 52454

Middle Eastern (MID) AF: 0.000868 AC: 5 AN: 5762

European-Non Finnish (NFE) AF: 0.00477 AC: 5294 AN: 1110066

Other (OTH) AF: 0.00251 AC: 151 AN: 60192

GnomAD4 genome AF: 0.00304 AC: 463 AN: 152388 Hom.: 0 Cov.: 33 AF XY: 0.00283 AC XY: 211 AN XY: 74530

African (AFR) AF: 0.000986 AC: 41 AN: 41596

American (AMR) AF: 0.00150 AC: 23 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4834

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00519 AC: 353 AN: 68036

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00459 Hom.: 0

Bravo AF: 0.00255

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Herpes simplex encephalitis, susceptibility to, 1 (3)
-	-	1	not specified (1)
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.39
PhyloP100		-0.38
Mutation Taster		=100/0	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: rs117183629; hg19: chr11-67767160;