rs182093266

Variant names:

• chr11-68003181-G-A
• rs182093266
• NM_030930.4:c.239-6C>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.239-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,609,584 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (5 hom.)
• Consequence: UNC93B1 NM_030930.4 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.236
• 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)

ENSG00000309414 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-68003181-G-A is Benign according to our data. Variant chr11-68003181-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 537939.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 = 0.00176 (268/152134) while in subpopulation NFE AF = 0.00284 (193/67960). AF 95% confidence interval is 0.00251. There are 0 homozygotes in GnomAd4. There are 138 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.239-6C>T		splice_region intron	N/A	NP_112192.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.239-6C>T		splice_region intron	N/A	ENSP00000227471.3
	UNC93B1	ENST00000528096.1	TSL:2	n.289C>T		non_coding_transcript_exon	Exon 1 of 2
	UNC93B1	ENST00000533424.6	TSL:5	n.727C>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes AF: 0.00176 AC: 268 AN: 152016 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00176 AC: 431 AN: 244594 AF XY: 0.00166

Gnomad AFR exome AF: 0.000521

Gnomad AMR exome AF: 0.00201

Gnomad ASJ exome AF: 0.00320

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00134

GnomAD4 exome AF: 0.00240 AC: 3496 AN: 1457450 Hom.: 5 Cov.: 31 AF XY: 0.00226 AC XY: 1636 AN XY: 725104

African (AFR) AF: 0.000508 AC: 17 AN: 33448

American (AMR) AF: 0.00197 AC: 88 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00379 AC: 99 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86134

European-Finnish (FIN) AF: 0.000878 AC: 44 AN: 50102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5536

European-Non Finnish (NFE) AF: 0.00278 AC: 3086 AN: 1111488

Other (OTH) AF: 0.00267 AC: 161 AN: 60274

GnomAD4 genome AF: 0.00176 AC: 268 AN: 152134 Hom.: 0 Cov.: 31 AF XY: 0.00186 AC XY: 138 AN XY: 74384

African (AFR) AF: 0.000433 AC: 18 AN: 41534

American (AMR) AF: 0.00183 AC: 28 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 67960

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00231 Hom.: 0

Bravo AF: 0.00193

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00178

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.7
DANN	Benign	0.95
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs182093266; hg19: chr11-67770651;