rs2240387

Positions:

• chr11-67995404-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC93B1	NM_030930.4	c.1363+207A>G		intron_variant		ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1	c.952+207A>G		intron_variant			XP_011543592.1
UNC93B1	XM_011545291.3	c.808+207A>G		intron_variant			XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7	c.1363+207A>G		intron_variant		1	NM_030930.4	ENSP00000227471.3
UNC93B1	ENST00000525368.1	n.370+207A>G		intron_variant		2

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

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.259

Alfa AF: 0.263 Hom.: 706

Bravo AF: 0.270

Asia WGS AF: 0.182 AC: 632 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.6
DANN	Benign	0.90

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: rs2240387; hg19: chr11-67762875;