19-54220691-T-C

Variant names:

• chr19-54220691-T-C
• rs756849617
• NM_006864.4:c.1095A>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_006864.4(LILRB3):​c.1095A>G​(p.Pro365Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 23)
  • Exomes 𝑓: 0.00015 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: LILRB3 NM_006864.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.90
• Publications: 0 publications found

Genes affected

LILRB3 (HGNC:6607): (leukocyte immunoglobulin like receptor B3) This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RPS9 (HGNC:10442): (ribosomal protein S9) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 40S subunit. The protein belongs to the S4P family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, multiple processed pseudogenes derived from this gene are dispersed through the genome. [provided by RefSeq, Jul 2008]

LOC124904768 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.11).
• BP6: Variant 19-54220691-T-C is Benign according to our data. Variant chr19-54220691-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2650429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-4.9 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006864.4. 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
	LILRB3	NM_006864.4	MANE Select	c.1095A>G	p.Pro365Pro	synonymous	Exon 6 of 13	NP_006855.3	C9JWL8
	LILRB3	NM_001320960.2		c.1095A>G	p.Pro365Pro	synonymous	Exon 6 of 14	NP_001307889.1
	LILRB3	NM_001081450.3		c.1095A>G	p.Pro365Pro	synonymous	Exon 6 of 13	NP_001074919.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LILRB3	ENST00000445347.2	TSL:2 MANE Select	c.1095A>G	p.Pro365Pro	synonymous	Exon 6 of 13	ENSP00000388199.2	C9JWL8
	LILRB3	ENST00000245620.13	TSL:1	c.1095A>G	p.Pro365Pro	synonymous	Exon 6 of 13	ENSP00000245620.9	O75022
	LILRB3	ENST00000414379.5	TSL:1	n.*602A>G		non_coding_transcript_exon	Exon 7 of 14	ENSP00000416920.1	F8WD89

Frequencies

GnomAD3 genomes AF: 0.000199 AC: 25 AN: 125328 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000837

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000334

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000825

Gnomad OTH AF: 0.000595

GnomAD2 exomes AF: 0.0000291 AC: 7 AN: 240842 AF XY: 0.0000232

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000955

Gnomad NFE exome AF: 0.00000911

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000150 AC: 210 AN: 1398792 Hom.: 6 Cov.: 75 AF XY: 0.000142 AC XY: 99 AN XY: 696400

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

African (AFR) AF: 0.00142 AC: 43 AN: 30300

American (AMR) AF: 0.000637 AC: 26 AN: 40810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25792

East Asian (EAS) AF: 0.000172 AC: 5 AN: 29000

South Asian (SAS) AF: 0.000241 AC: 20 AN: 82970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52758

Middle Eastern (MID) AF: 0.000357 AC: 2 AN: 5608

European-Non Finnish (NFE) AF: 0.0000913 AC: 98 AN: 1073958

Other (OTH) AF: 0.000278 AC: 16 AN: 57596

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000207 AC: 26 AN: 125384 Hom.: 0 Cov.: 23 AF XY: 0.000229 AC XY: 14 AN XY: 61240

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

African (AFR) AF: 0.000568 AC: 17 AN: 29916

American (AMR) AF: 0.0000837 AC: 1 AN: 11952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3302

East Asian (EAS) AF: 0.000335 AC: 1 AN: 2982

South Asian (SAS) AF: 0.00 AC: 0 AN: 4142

European-Finnish (FIN) AF: 0.000102 AC: 1 AN: 9814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000825 AC: 5 AN: 60572

Other (OTH) AF: 0.000593 AC: 1 AN: 1686

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000135731), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.60
DANN	Benign	0.18
PhyloP100		-4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs756849617; hg19: chr19-54724561;