Variant rs144979304 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000227471.7(UNC93B1):c.907-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,539,932 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0039 ( 19 hom. )

Consequence

UNC93B1
ENST00000227471.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.498

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 11-67996789-G-A is Benign according to our data. Variant chr11-67996789-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 537924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
UNC93B1	NM_030930.4 linkuse as main transcript	c.907-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000227471.7	NP_112192.2
UNC93B1	XM_011545290.1 linkuse as main transcript	c.496-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_011543592.1
UNC93B1	XM_011545291.3 linkuse as main transcript	c.352-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 linkuse as main transcript	c.907-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_030930.4	ENSP00000227471	P1
UNC93B1	ENST00000533424.6 linkuse as main transcript	n.1401-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00312

AC:

475

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00364

AC:

610

AN:

167386

Hom.:

AF XY:

0.00342

AC XY:

308

AN XY:

90062

show subpopulations

Gnomad AFR exome

AF:

0.000884

Gnomad AMR exome

AF:

0.000793

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000762

Gnomad FIN exome

AF:

0.00626

Gnomad NFE exome

AF:

0.00388

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00390

AC:

5406

AN:

1387632

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

2630

AN XY:

681588

show subpopulations

Gnomad4 AFR exome

AF:

0.000670

Gnomad4 AMR exome

AF:

0.000870

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000573

Gnomad4 FIN exome

AF:

0.00659

Gnomad4 NFE exome

AF:

0.00395

Gnomad4 OTH exome

AF:

0.00428

GnomAD4 genome

AF:

0.00313

AC:

476

AN:

152300

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.00440

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00471

Hom.:

Bravo

AF:

0.00279

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

UNC93B1: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.81

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