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 Benign/Likely_benign. ClinVar VariationId is 470494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.1724_1725delCCinsAG	p.Pro575Gln	missense	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.1724_1725delCCinsAG	p.Pro575Gln	missense	N/A	ENSP00000227471.3
	UNC93B1	ENST00000864508.1		c.1763_1764delCCinsAG	p.Pro588Gln	missense	N/A	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1748_1749delCCinsAG	p.Pro583Gln	missense	N/A	ENSP00000534568.1

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

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Herpes simplex encephalitis, susceptibility to, 1 (2)

Computational scores

Source: dbNSFP v4.9

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;