11-67997585-T-A

Variant names:

• chr11-67997585-T-A
• rs308328
• NM_030930.4:c.906+90A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030930.4(UNC93B1):​c.906+90A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UNC93B1 NM_030930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.906+90A>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.906+90A>T		intron	N/A	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.945+90A>T		intron	N/A	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.930+90A>T		intron	N/A	ENSP00000534568.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1421718 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 704586

African (AFR) AF: 0.00 AC: 0 AN: 32962

American (AMR) AF: 0.00 AC: 0 AN: 43662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24988

East Asian (EAS) AF: 0.00 AC: 0 AN: 39224

South Asian (SAS) AF: 0.00 AC: 0 AN: 83436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097018

Other (OTH) AF: 0.00 AC: 0 AN: 59070

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.53
DANN	Benign	0.65
PhyloP100		-1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs308328; hg19: chr11-67765056;