Variant 11-67991783-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_030930.4(UNC93B1):c.1557C>G(p.Arg519Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,433,224 control chromosomes in the GnomAD database, including 45,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 6376 hom., cov: 34)

Exomes 𝑓: 0.24 ( 39511 hom. )

Consequence

UNC93B1
NM_030930.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0730

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:

UNC93B1 (HGNC:):

UNC93B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-67991783-G-C is Benign according to our data. Variant chr11-67991783-G-C is described in ClinVar as [Benign]. Clinvar id is 537932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.073 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC93B1	NM_030930.4 linkuse as main transcript	c.1557C>G	p.Arg519Arg	synonymous_variant	11/11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 linkuse as main transcript	c.1146C>G	p.Arg382Arg	synonymous_variant	9/9		XP_011543592.1
UNC93B1	XM_011545291.3 linkuse as main transcript	c.1002C>G	p.Arg334Arg	synonymous_variant	8/8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.1557C>G	p.Arg519Arg	synonymous_variant	11/11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000525368.1 linkuse as main transcript	n.*35C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

42262

AN:

125786

Hom.:

6375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.448

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.331

GnomAD3 exomes

AF:

0.122

AC:

14620

AN:

119604

Hom.:

1847

AF XY:

0.114

AC XY:

7370

AN XY:

64878

show subpopulations

Gnomad AFR exome

AF:

0.384

Gnomad AMR exome

AF:

0.0816

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.146

Gnomad SAS exome

AF:

0.0610

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.139

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

AF:

0.244

AC:

318737

AN:

1307336

Hom.:

39511

Cov.:

AF XY:

0.241

AC XY:

155403

AN XY:

645510

show subpopulations

Gnomad4 AFR exome

AF:

0.415

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.254

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.336

AC:

42303

AN:

125888

Hom.:

6376

Cov.:

AF XY:

0.328

AC XY:

19999

AN XY:

60966

show subpopulations

Gnomad4 AFR

AF:

0.448

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.262

Hom.:

906

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 26% of patients studied by a panel of primary immunodeficiencies. Number of patients: 25. Only high quality variants are reported. -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

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