rs7149

Variant names:

• chr11-67991783-G-C
• rs7149
• NM_030930.4:c.1557C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-67991783-G-C
• chr11-67991783-G-A
• chr11-67991783-G-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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0730
• Publications: 7 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=-0.81).
• BP6: Variant 11-67991783-G-C is Benign according to our data. Variant chr11-67991783-G-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.1557C>G	p.Arg519Arg	synonymous	Exon 11 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.1557C>G	p.Arg519Arg	synonymous	Exon 11 of 11	ENSP00000227471.3	Q9H1C4
	UNC93B1	ENST00000864508.1		c.1596C>G	p.Arg532Arg	synonymous	Exon 11 of 11	ENSP00000534567.1
	UNC93B1	ENST00000864509.1		c.1581C>G	p.Arg527Arg	synonymous	Exon 11 of 11	ENSP00000534568.1

Frequencies

GnomAD3 genomes AF: 0.336 AC: 42262 AN: 125786 Hom.: 6375 Cov.: 34

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

GnomAD2 exomes AF: 0.122 AC: 14620 AN: 119604 AF XY: 0.114

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 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.: 37 AF XY: 0.241 AC XY: 155403 AN XY: 645510

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.415 AC: 12508 AN: 30110

American (AMR) AF: 0.135 AC: 4591 AN: 34048

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 6513 AN: 23130

East Asian (EAS) AF: 0.165 AC: 5710 AN: 34562

South Asian (SAS) AF: 0.140 AC: 10534 AN: 75464

European-Finnish (FIN) AF: 0.183 AC: 5642 AN: 30862

Middle Eastern (MID) AF: 0.247 AC: 947 AN: 3840

European-Non Finnish (NFE) AF: 0.254 AC: 258785 AN: 1020702

Other (OTH) AF: 0.247 AC: 13507 AN: 54618

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.336 AC: 42303 AN: 125888 Hom.: 6376 Cov.: 34 AF XY: 0.328 AC XY: 19999 AN XY: 60966

African (AFR) AF: 0.448 AC: 17108 AN: 38202

American (AMR) AF: 0.235 AC: 2945 AN: 12550

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 920 AN: 2726

East Asian (EAS) AF: 0.200 AC: 912 AN: 4558

South Asian (SAS) AF: 0.193 AC: 722 AN: 3738

European-Finnish (FIN) AF: 0.216 AC: 1621 AN: 7514

Middle Eastern (MID) AF: 0.268 AC: 73 AN: 272

European-Non Finnish (NFE) AF: 0.318 AC: 17143 AN: 53882

Other (OTH) AF: 0.330 AC: 575 AN: 1744

Alfa AF: 0.262 Hom.: 906

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		0.073
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: rs7149; hg19: chr11-67759254; COSMIC: COSV57097580; COSMIC: COSV57097580;