rs2375183

chr11-67991561-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_030930.4(UNC93B1):c.1779G>A(p.Gly593=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,469,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: UNC93B1 NM_030930.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 11-67991561-C-T is Benign according to our data. Variant chr11-67991561-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 537940.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.1779G>A	p.Gly593=	synonymous_variant	11/11	ENST00000227471.7
UNC93B1	XM_011545290.1	c.1368G>A	p.Gly456=	synonymous_variant	9/9
UNC93B1	XM_011545291.3	c.1224G>A	p.Gly408=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1779G>A	p.Gly593=	synonymous_variant	11/11	1	NM_030930.4	P1

Frequencies

GnomAD3 genomes AF: 0.000520 AC: 79 AN: 151920 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000736

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000483 AC: 4 AN: 82760 Hom.: 0 AF XY: 0.0000431 AC XY: 2 AN XY: 46452

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.0000633

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000643

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000660 AC: 87 AN: 1317558 Hom.: 0 Cov.: 30 AF XY: 0.0000541 AC XY: 35 AN XY: 646676

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.0000739

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000557

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000305

Gnomad4 OTH exome AF: 0.0000366

GnomAD4 genome AF: 0.000520 AC: 79 AN: 152036 Hom.: 0 Cov.: 33 AF XY: 0.000457 AC XY: 34 AN XY: 74342

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000737

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000674 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 09, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.5
Dann	Benign	0.94

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: rs2375183; hg19: chr11-67759032;