Genetic Variant UNC93B1:c.907-5C>A (chr11-67996789-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030930.4(UNC93B1):c.907-5C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

UNC93B1
NM_030930.4 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UNC93B1	NM_030930.4 link	c.907-5C>A	splice_region_variant, intron_variant	Intron 7 of 10	ENST00000227471.7	NP_112192.2	Q9H1C4
UNC93B1	XM_011545290.1 link	c.496-5C>A	splice_region_variant, intron_variant	Intron 5 of 8		XP_011543592.1
UNC93B1	XM_011545291.3 link	c.352-5C>A	splice_region_variant, intron_variant	Intron 4 of 7		XP_011543593.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC93B1	ENST00000227471.7 link	c.907-5C>A		splice_region_variant, intron_variant	Intron 7 of 10	1	NM_030930.4	ENSP00000227471.3		Q9H1C4
UNC93B1	ENST00000533424.6 link	n.1401-5C>A		splice_region_variant, intron_variant	Intron 6 of 6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.21e-7

AC:

AN:

1387640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.40

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.40

Position offset: -2

DS_AL_spliceai

0.34

Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over