rs112284414

Variant names:

• chr11-67995768-C-G
• rs112284414
• NM_030930.4:c.1206G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-67995768-C-G
• chr11-67995768-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_030930.4(UNC93B1):​c.1206G>C​(p.Pro402Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,547,488 control chromosomes in the GnomAD database, including 511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P402P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.026 (139 hom., cov: 29)
  • Exomes 𝑓: 0.010 (372 hom.)
• Consequence: UNC93B1 NM_030930.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.812
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• herpes simplex encephalitis, susceptibility to, 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• systemic lupus erythematosus

  Inheritance: SD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-67995768-C-G is Benign according to our data. Variant chr11-67995768-C-G is described in ClinVar as Benign. ClinVar VariationId is 470489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.812 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030930.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	NM_030930.4	MANE Select	c.1206G>C	p.Pro402Pro	synonymous	Exon 9 of 11	NP_112192.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UNC93B1	ENST00000227471.7	TSL:1 MANE Select	c.1206G>C	p.Pro402Pro	synonymous	Exon 9 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.1245G>C	p.Pro415Pro	synonymous	Exon 9 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1230G>C	p.Pro410Pro	synonymous	Exon 9 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3975 AN: 151758 Hom.: 138 Cov.: 29

Gnomad AFR AF: 0.0731

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.0182 AC: 2736 AN: 149964 AF XY: 0.0213

Gnomad AFR exome AF: 0.0723

Gnomad AMR exome AF: 0.00516

Gnomad ASJ exome AF: 0.00431

Gnomad EAS exome AF: 0.0195

Gnomad FIN exome AF: 0.000431

Gnomad NFE exome AF: 0.00452

Gnomad OTH exome AF: 0.00979

GnomAD4 exome AF: 0.0104 AC: 14518 AN: 1395612 Hom.: 372 Cov.: 36 AF XY: 0.0120 AC XY: 8257 AN XY: 688416

African (AFR) AF: 0.0767 AC: 2417 AN: 31522

American (AMR) AF: 0.00619 AC: 221 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00513 AC: 129 AN: 25156

East Asian (EAS) AF: 0.0301 AC: 1075 AN: 35744

South Asian (SAS) AF: 0.0669 AC: 5291 AN: 79130

European-Finnish (FIN) AF: 0.000353 AC: 17 AN: 48116

Middle Eastern (MID) AF: 0.00714 AC: 29 AN: 4062

European-Non Finnish (NFE) AF: 0.00416 AC: 4490 AN: 1078390

Other (OTH) AF: 0.0147 AC: 849 AN: 57782

GnomAD4 genome AF: 0.0263 AC: 3999 AN: 151876 Hom.: 139 Cov.: 29 AF XY: 0.0261 AC XY: 1940 AN XY: 74228

African (AFR) AF: 0.0736 AC: 3040 AN: 41328

American (AMR) AF: 0.0106 AC: 162 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00519 AC: 18 AN: 3470

East Asian (EAS) AF: 0.0259 AC: 133 AN: 5132

South Asian (SAS) AF: 0.0704 AC: 340 AN: 4828

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00415 AC: 282 AN: 67922

Other (OTH) AF: 0.00995 AC: 21 AN: 2110

Alfa AF: 0.00392 Hom.: 1

Bravo AF: 0.0273

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Herpes simplex encephalitis, susceptibility to, 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.19
DANN	Benign	0.74
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs112284414; hg19: chr11-67763239;