rs308328

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-67997585-T-C
• chr11-67997585-T-A
• chr11-67997585-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030930.4(UNC93B1):​c.906+90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,573,126 control chromosomes in the GnomAD database, including 161,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (25002 hom., cov: 34)
  • Exomes 𝑓: 0.43 (136815 hom.)
• Consequence: UNC93B1 NM_030930.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.16
• Publications: 21 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-67997585-T-C is Benign according to our data. Variant chr11-67997585-T-C is described in ClinVar as Benign. ClinVar VariationId is 2688062.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81518 AN: 152076 Hom.: 24942 Cov.: 34

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.431 AC: 612739 AN: 1420932 Hom.: 136815 Cov.: 30 AF XY: 0.430 AC XY: 302587 AN XY: 704182

African (AFR) AF: 0.866 AC: 28531 AN: 32948

American (AMR) AF: 0.285 AC: 12415 AN: 43632

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 11681 AN: 24962

East Asian (EAS) AF: 0.390 AC: 15279 AN: 39206

South Asian (SAS) AF: 0.390 AC: 32552 AN: 83380

European-Finnish (FIN) AF: 0.348 AC: 12951 AN: 37236

Middle Eastern (MID) AF: 0.459 AC: 1873 AN: 4080

European-Non Finnish (NFE) AF: 0.430 AC: 471218 AN: 1096462

Other (OTH) AF: 0.445 AC: 26239 AN: 59026

GnomAD4 genome AF: 0.536 AC: 81634 AN: 152194 Hom.: 25002 Cov.: 34 AF XY: 0.524 AC XY: 39016 AN XY: 74406

African (AFR) AF: 0.853 AC: 35433 AN: 41552

American (AMR) AF: 0.386 AC: 5901 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.418 AC: 2159 AN: 5160

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4826

European-Finnish (FIN) AF: 0.321 AC: 3395 AN: 10590

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29458 AN: 67990

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.469 Hom.: 47651

Bravo AF: 0.552

Asia WGS AF: 0.422 AC: 1469 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.68
DANN	Benign	0.38
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV57100252; COSMIC: COSV57100252;