Variant chr11-67991615-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_StrongBP7BS1BS2

The NM_030930.4(UNC93B1):c.1725C>G(p.Pro575Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00886 in 1,499,800 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0092 ( 68 hom. )

Consequence

UNC93B1
NM_030930.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.62

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-67991615-G-C is Benign according to our data. Variant chr11-67991615-G-C is described in ClinVar as [Benign]. Clinvar id is 782776.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67991615-G-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-1.62 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00591 (899/152182) while in subpopulation NFE AF= 0.00917 (623/67948). AF 95% confidence interval is 0.00857. There are 6 homozygotes in gnomad4. There are 420 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.1725C>G	p.Pro575Pro	synonymous_variant	11/11	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.1314C>G	p.Pro438Pro	synonymous_variant	9/9		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.1170C>G	p.Pro390Pro	synonymous_variant	8/8		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.1725C>G	p.Pro575Pro	synonymous_variant	11/11	1	NM_030930.4	ENSP00000227471.3		Q9H1C4

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00210

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00863

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00917

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00609

AC:

582

AN:

95542

Hom.:

AF XY:

0.00603

AC XY:

323

AN XY:

53596

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.00587

Gnomad ASJ exome

AF:

0.00431

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00185

Gnomad FIN exome

AF:

0.00196

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00995

GnomAD4 exome

AF:

0.00919

AC:

12387

AN:

1347618

Hom.:

Cov.:

AF XY:

0.00892

AC XY:

5924

AN XY:

664088

show subpopulations

Gnomad4 AFR exome

AF:

0.00127

Gnomad4 AMR exome

AF:

0.00574

Gnomad4 ASJ exome

AF:

0.00392

Gnomad4 EAS exome

AF:

0.0000303

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00214

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00782

GnomAD4 genome

AF:

0.00591

AC:

899

AN:

152182

Hom.:

Cov.:

AF XY:

0.00565

AC XY:

420

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00209

Gnomad4 AMR

AF:

0.00862

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00917

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00649

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	UNC93B1: BP4, BP7, BS1, BS2 -

Herpes simplex encephalitis, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

DANN

Benign

0.53

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