rs760132599

chr11-67995888-C-CG

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_030930.4(UNC93B1):c.1090-5_1090-4insC variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000534 in 1,497,598 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: UNC93B1 NM_030930.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-67995888-C-CG is Benign according to our data. Variant chr11-67995888-C-CG is described in ClinVar as [Benign]. Clinvar id is 537933.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UNC93B1	NM_030930.4	c.1090-5_1090-4insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000227471.7
UNC93B1	XM_011545290.1	c.679-5_679-4insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
UNC93B1	XM_011545291.3	c.535-5_535-4insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1090-5_1090-4insC		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030930.4	P1
UNC93B1	ENST00000525368.1	n.92_93insC		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151738 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000297 AC: 4 AN: 1345860 Hom.: 0 Cov.: 35 AF XY: 0.00000152 AC XY: 1 AN XY: 659752

Gnomad4 AFR exome AF: 0.0000329

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000284

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000264 AC: 4 AN: 151738 Hom.: 0 Cov.: 29 AF XY: 0.0000135 AC XY: 1 AN XY: 74106

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000340

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2022

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs760132599; hg19: chr11-67763359;