Variant 11-67993705-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030930.4(UNC93B1):c.1453G>A(p.Val485Met) variant causes a missense change. The variant allele was found at a frequency of 0.00273 in 1,258,826 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 17 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.64

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=0.013433933).

BP6

Variant 11-67993705-C-T is Benign according to our data. Variant chr11-67993705-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 470491.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67993705-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00275 (3043/1106496) while in subpopulation MID AF= 0.0287 (101/3522). AF 95% confidence interval is 0.0241. There are 17 homozygotes in gnomad4_exome. There are 1656 alleles in male gnomad4_exome subpopulation. Median coverage is 15. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UNC93B1	NM_030930.4 linkuse as main transcript	c.1453G>A	p.Val485Met	missense_variant	10/11	ENST00000227471.7
UNC93B1	XM_011545290.1 linkuse as main transcript	c.1042G>A	p.Val348Met	missense_variant	8/9
UNC93B1	XM_011545291.3 linkuse as main transcript	c.898G>A	p.Val300Met	missense_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.1453G>A	p.Val485Met	missense_variant	10/11	1	NM_030930.4	P1
UNC93B1	ENST00000525368.1 linkuse as main transcript	n.460G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

396

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00287

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00422

AC:

600

AN:

142166

Hom.:

AF XY:

0.00456

AC XY:

347

AN XY:

76140

show subpopulations

Gnomad AFR exome

AF:

0.000281

Gnomad AMR exome

AF:

0.00533

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00568

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00311

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.00275

AC:

3043

AN:

1106496

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

1656

AN XY:

558282

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00579

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00209

Gnomad4 OTH exome

AF:

0.00473

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152330

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00287

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00534

Hom.:

Bravo

AF:

0.00308

ExAC

AF:

0.00150

AC:

145

ClinVar

Significance: Benign/Likely 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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 26, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

UNC93B1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.013

MetaSVM

Uncertain

0.054

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.70

REVEL

Uncertain

0.42

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.51

MVP

0.29

MPC

1.3

ClinPred

0.025

GERP RS

5.0

Varity_R

0.26

gMVP

0.87

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