dbSNP rs11543208: UNC93B1:p.Ala388Val (chr11-67995811-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030930.4(UNC93B1):c.1163C>T(p.Ala388Val) variant causes a missense change. The variant allele was found at a frequency of 0.0159 in 1,546,586 control chromosomes in the GnomAD database, including 206 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 29)

Exomes 𝑓: 0.016 ( 186 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.75

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004144609).

BP6

Variant 11-67995811-G-A is Benign according to our data. Variant chr11-67995811-G-A is described in ClinVar as [Benign]. Clinvar id is 470488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0117 (1781/152130) while in subpopulation NFE AF= 0.0172 (1170/67962). AF 95% confidence interval is 0.0164. There are 20 homozygotes in gnomad4. There are 865 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1163C>T	p.Ala388Val	missense_variant	Exon 9 of 11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.752C>T	p.Ala251Val	missense_variant	Exon 7 of 9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.608C>T	p.Ala203Val	missense_variant	Exon 6 of 8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.1163C>T	p.Ala388Val	missense_variant	Exon 9 of 11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 link	n.170C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1783

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.0253

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.0158

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0125

GnomAD3 exomes

AF:

0.0141

AC:

2054

AN:

145576

Hom.:

AF XY:

0.0146

AC XY:

1146

AN XY:

78434

show subpopulations

Gnomad AFR exome

AF:

0.00256

Gnomad AMR exome

AF:

0.00568

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.0000948

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0193

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0163

AC:

22789

AN:

1394456

Hom.:

186

Cov.:

AF XY:

0.0166

AC XY:

11403

AN XY:

687776

show subpopulations

Gnomad4 AFR exome

AF:

0.00225

Gnomad4 AMR exome

AF:

0.00620

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.0175

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0117

AC:

1781

AN:

152130

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

865

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00294

Gnomad4 AMR

AF:

0.00621

Gnomad4 ASJ

AF:

0.0253

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.0156

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0179

Hom.:

Bravo

AF:

0.0105

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00302

AC:

ESP6500EA

AF:

0.0114

AC:

ExAC

AF:

0.00654

AC:

542

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.059

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.4

REVEL

Benign

0.23

Sift

Benign

0.047

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.16

MPC

0.42

ClinPred

0.0039

GERP RS

2.9

Varity_R

0.016

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over