19-51746419-A-G

Variant names:

• chr19-51746419-A-G
• rs1042229
• NM_002029.4:c.576T>C

Variant summary

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

The NM_002029.4(FPR1):​c.576T>C​(p.Asn192Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,613,884 control chromosomes in the GnomAD database, including 14,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1184 hom., cov: 31)
  • Exomes 𝑓: 0.13 (12869 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.296
• Publications: 52 publications found

Genes affected

FPR1 (HGNC:3826): (formyl peptide receptor 1) This gene encodes a G protein-coupled receptor of mammalian phagocytic cells that is a member of the G-protein coupled receptor 1 family. The protein mediates the response of phagocytic cells to invasion of the host by microorganisms and is important in host defense and inflammation.[provided by RefSeq, Jul 2010]

FPR1 Gene-Disease associations (from GenCC):

• susceptibility to localized juvenile periodontitis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-51746419-A-G is Benign according to our data. Variant chr19-51746419-A-G is described in ClinVar as Benign. ClinVar VariationId is 1168164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.296 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002029.4. 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
	FPR1	NM_002029.4	MANE Select	c.576T>C	p.Asn192Asn	synonymous	Exon 2 of 2	NP_002020.1
	FPR1	NM_001193306.2		c.576T>C	p.Asn192Asn	synonymous	Exon 3 of 3	NP_001180235.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.576T>C	p.Asn192Asn	synonymous	Exon 2 of 2	ENSP00000302707.3
	FPR1	ENST00000594900.2	TSL:4	c.576T>C	p.Asn192Asn	synonymous	Exon 3 of 3	ENSP00000470750.2
	FPR1	ENST00000595042.5	TSL:2	c.576T>C	p.Asn192Asn	synonymous	Exon 3 of 3	ENSP00000471493.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18361 AN: 151898 Hom.: 1184 Cov.: 31

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0989

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.122

GnomAD2 exomes AF: 0.132 AC: 33056 AN: 251308 AF XY: 0.135

Gnomad AFR exome AF: 0.0839

Gnomad AMR exome AF: 0.0840

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.196

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.129 AC: 189146 AN: 1461868 Hom.: 12869 Cov.: 70 AF XY: 0.131 AC XY: 94974 AN XY: 727236

African (AFR) AF: 0.0840 AC: 2812 AN: 33480

American (AMR) AF: 0.0865 AC: 3867 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 3121 AN: 26136

East Asian (EAS) AF: 0.161 AC: 6384 AN: 39700

South Asian (SAS) AF: 0.179 AC: 15403 AN: 86258

European-Finnish (FIN) AF: 0.165 AC: 8810 AN: 53416

Middle Eastern (MID) AF: 0.0862 AC: 497 AN: 5766

European-Non Finnish (NFE) AF: 0.126 AC: 140267 AN: 1111992

Other (OTH) AF: 0.132 AC: 7985 AN: 60396

GnomAD4 genome AF: 0.121 AC: 18366 AN: 152016 Hom.: 1184 Cov.: 31 AF XY: 0.125 AC XY: 9271 AN XY: 74310

African (AFR) AF: 0.0882 AC: 3655 AN: 41458

American (AMR) AF: 0.0989 AC: 1512 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 414 AN: 3464

East Asian (EAS) AF: 0.198 AC: 1018 AN: 5140

South Asian (SAS) AF: 0.177 AC: 851 AN: 4816

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10572

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8616 AN: 67956

Other (OTH) AF: 0.123 AC: 261 AN: 2116

Alfa AF: 0.00485 Hom.: 41618

EpiCase AF: 0.123

EpiControl AF: 0.123

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Gingival disorder (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.87
DANN	Benign	0.41
PhyloP100		0.30
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: rs1042229; hg19: chr19-52249672; COSMIC: COSV59051368; COSMIC: COSV59051368;