rs2240387

Variant names:

• chr11-67995404-T-C
• rs2240387
• NM_030930.4:c.1363+207A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030930.4(UNC93B1):​c.1363+207A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,874 control chromosomes in the GnomAD database, including 5,701 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5701 hom., cov: 31)
• Consequence: UNC93B1 NM_030930.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.590
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.1363+207A>G		intron	N/A	NP_112192.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.1363+207A>G		intron	N/A	ENSP00000227471.3
	UNC93B1	ENST00000525368.1	TSL:2	n.370+207A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39656 AN: 151756 Hom.: 5701 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.261 AC: 39690 AN: 151874 Hom.: 5701 Cov.: 31 AF XY: 0.251 AC XY: 18638 AN XY: 74204

African (AFR) AF: 0.371 AC: 15349 AN: 41370

American (AMR) AF: 0.185 AC: 2826 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3468

East Asian (EAS) AF: 0.161 AC: 829 AN: 5154

South Asian (SAS) AF: 0.142 AC: 685 AN: 4816

European-Finnish (FIN) AF: 0.137 AC: 1456 AN: 10610

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16764 AN: 67892

Other (OTH) AF: 0.259 AC: 543 AN: 2100

Alfa AF: 0.255 Hom.: 1514

Bravo AF: 0.270

Asia WGS AF: 0.182 AC: 632 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.6
DANN	Benign	0.90
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240387; hg19: chr11-67762875;