rs1554984685

Variant names:

• chr11-67991615-GG-CT
• rs1554984685
• NM_030930.4:c.1724_1725delCCinsAG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_030930.4(UNC93B1):​c.1724_1725delCCinsAG​(p.Pro575Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. The variant is present in control chromosomes in GnomAd MNV project. The variant allele was found at a frequency of 0.00576 in 730 alleles, including 4 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P575H) has been classified as Likely benign.

• Frequency: GnomAD MNV: 𝑓 0.0058 Genomes: not found (cov: 33)
• Consequence: UNC93B1 NM_030930.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.49
• 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)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP6: Variant 11-67991615-GG-CT is Benign according to our data. Variant chr11-67991615-GG-CT is described in ClinVar as [Likely_benign]. Clinvar id is 470494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.1724_1725delCCinsAG	p.Pro575Gln	missense_variant		ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1	c.1313_1314delCCinsAG	p.Pro438Gln	missense_variant			XP_011543592.1
UNC93B1	XM_011545291.3	c.1169_1170delCCinsAG	p.Pro390Gln	missense_variant			XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1724_1725delCCinsAG	p.Pro575Gln	missense_variant		1	NM_030930.4	ENSP00000227471.3
UNC93B1	ENST00000525368.1	n.*202_*203delCCinsAG		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

GnomAD MNV AF: 0.00576 AC: 730 Hom.: 4

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1 Benign:2

Apr 15, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554984685; hg19: chr11-67759086; COSMIC: COSV57100447; COSMIC: COSV57100447;