NM_002029.4:c.993C>T

Variant names:

• chr19-51746002-G-A
• rs17849971
• NM_002029.4:c.993C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_002029.4(FPR1):​c.993C>T​(p.Thr331Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0273 in 1,614,118 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (49 hom., cov: 32)
  • Exomes 𝑓: 0.028 (727 hom.)
• Consequence: FPR1 NM_002029.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.327
• Publications: 7 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=-0.82).
• BP6: Variant 19-51746002-G-A is Benign according to our data. Variant chr19-51746002-G-A is described in ClinVar as Benign. ClinVar VariationId is 402875.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.327 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0204 (3102/152246) while in subpopulation NFE AF = 0.0318 (2163/68008). AF 95% confidence interval is 0.0307. There are 49 homozygotes in GnomAd4. There are 1515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR,Unknown gene

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.993C>T	p.Thr331Thr	synonymous	Exon 2 of 2	NP_002020.1	P21462
	FPR1	NM_001193306.2		c.993C>T	p.Thr331Thr	synonymous	Exon 3 of 3	NP_001180235.1	P21462

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FPR1	ENST00000304748.5	TSL:1 MANE Select	c.993C>T	p.Thr331Thr	synonymous	Exon 2 of 2	ENSP00000302707.3	P21462
	FPR1	ENST00000594900.2	TSL:4	c.993C>T	p.Thr331Thr	synonymous	Exon 3 of 3	ENSP00000470750.2	P21462
	FPR1	ENST00000595042.5	TSL:2	c.993C>T	p.Thr331Thr	synonymous	Exon 3 of 3	ENSP00000471493.1	P21462

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3101 AN: 152128 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.0421

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.0210 AC: 5283 AN: 251282 AF XY: 0.0211

Gnomad AFR exome AF: 0.00560

Gnomad AMR exome AF: 0.00810

Gnomad ASJ exome AF: 0.00933

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0426

Gnomad NFE exome AF: 0.0308

Gnomad OTH exome AF: 0.0212

GnomAD4 exome AF: 0.0280 AC: 40904 AN: 1461872 Hom.: 727 Cov.: 71 AF XY: 0.0276 AC XY: 20096 AN XY: 727232

African (AFR) AF: 0.00451 AC: 151 AN: 33480

American (AMR) AF: 0.00834 AC: 373 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00957 AC: 250 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00878 AC: 757 AN: 86256

European-Finnish (FIN) AF: 0.0398 AC: 2125 AN: 53420

Middle Eastern (MID) AF: 0.00520 AC: 30 AN: 5768

European-Non Finnish (NFE) AF: 0.0321 AC: 35665 AN: 1111992

Other (OTH) AF: 0.0257 AC: 1552 AN: 60396

GnomAD4 genome AF: 0.0204 AC: 3102 AN: 152246 Hom.: 49 Cov.: 32 AF XY: 0.0203 AC XY: 1515 AN XY: 74452

African (AFR) AF: 0.00580 AC: 241 AN: 41564

American (AMR) AF: 0.0106 AC: 162 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4826

European-Finnish (FIN) AF: 0.0421 AC: 447 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0318 AC: 2163 AN: 68008

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.0249 Hom.: 50

Bravo AF: 0.0176

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0271

EpiControl AF: 0.0278

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		0.33
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: rs17849971; hg19: chr19-52249255;