rs751962660

Variant names:

• chr11-67995854-G-C
• rs751962660
• NM_030930.4:c.1120C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-67995854-G-C
• chr11-67995854-G-A
• chr11-67995854-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_030930.4(UNC93B1):​c.1120C>G​(p.Arg374Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R374Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000075 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UNC93B1 NM_030930.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• 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)
• systemic lupus erythematosus

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04690677).

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.1120C>G	p.Arg374Gly	missense	Exon 9 of 11	NP_112192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.1120C>G	p.Arg374Gly	missense	Exon 9 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.1159C>G	p.Arg387Gly	missense	Exon 9 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1144C>G	p.Arg382Gly	missense	Exon 9 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151830 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000749 AC: 1 AN: 133554 AF XY: 0.00

Gnomad AFR exome AF: 0.000153

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000752 AC: 104 AN: 1383032 Hom.: 0 Cov.: 36 AF XY: 0.0000689 AC XY: 47 AN XY: 681748

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00309 AC: 94 AN: 30376

American (AMR) AF: 0.00 AC: 0 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24536

East Asian (EAS) AF: 0.00 AC: 0 AN: 35684

South Asian (SAS) AF: 0.00 AC: 0 AN: 78220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42508

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075180

Other (OTH) AF: 0.000174 AC: 10 AN: 57396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151830 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74144

African (AFR) AF: 0.00 AC: 0 AN: 41310

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67914

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ExAC AF: 0.000121 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.4
PrimateAI	Benign	0.41	T
REVEL	Benign	0.21
Sift4G	Benign	0.21	T
Polyphen		0.057	B
Vest4		0.33
MutPred		0.60		Loss of methylation at R374 (P = 0.0185)
MVP		0.11
MPC		0.62
ClinPred		0.068	T
GERP RS		1.9
Varity_R		0.19
gMVP		0.40
Mutation Taster		=87/13	polymorphism

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: rs751962660; hg19: chr11-67763325;