chr11-67991572-C-A

Position:

chr11-67991572-C-A

Variant summary

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

The NM_030930.4(UNC93B1):c.1768G>T(p.Gly590Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00449 in 1,488,914 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G590R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0089 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 27 hom. )

Consequence

UNC93B1
NM_030930.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.38

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=0.0035933256).

BP6

Variant 11-67991572-C-A is Benign according to our data. Variant chr11-67991572-C-A is described in ClinVar as [Benign]. Clinvar id is 470495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00888 (1351/152056) while in subpopulation AFR AF= 0.0232 (962/41536). AF 95% confidence interval is 0.0219. There are 12 homozygotes in gnomad4. There are 652 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UNC93B1	NM_030930.4 linkuse as main transcript	c.1768G>T	p.Gly590Trp	missense_variant	11/11	ENST00000227471.7
UNC93B1	XM_011545290.1 linkuse as main transcript	c.1357G>T	p.Gly453Trp	missense_variant	9/9
UNC93B1	XM_011545291.3 linkuse as main transcript	c.1213G>T	p.Gly405Trp	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.1768G>T	p.Gly590Trp	missense_variant	11/11	1	NM_030930.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00887

AC:

1347

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00426

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00290

AC:

269

AN:

92742

Hom.:

AF XY:

0.00255

AC XY:

132

AN XY:

51842

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00266

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.000176

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00399

AC:

5336

AN:

1336858

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2557

AN XY:

658162

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.00316

Gnomad4 EAS exome

AF:

0.000345

Gnomad4 SAS exome

AF:

0.000230

Gnomad4 FIN exome

AF:

0.000332

Gnomad4 NFE exome

AF:

0.00382

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.00888

AC:

1351

AN:

152056

Hom.:

Cov.:

AF XY:

0.00877

AC XY:

652

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0232

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00426

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.0102

ExAC

AF:

0.00124

AC:

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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.054

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

MutationTaster

Benign

0.98

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.35

MutPred

0.47

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.043

MPC

1.3

ClinPred

0.027

GERP RS

4.6

Varity_R

0.18

gMVP

0.38

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