dbSNP rs61749608: F2RL1:p.Arg2Arg (chr5-76819186-C-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005242.6(F2RL1):c.4C>A(p.Arg2Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,581,128 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 74 hom. )

Consequence

F2RL1
NM_005242.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.209

Publications

0 publications found

Variant links:

Genes affected

F2RL1 (HGNC:3538): (F2R like trypsin receptor 1) This gene encodes a member of the G-protein coupled receptor 1 family of proteins. The encoded cell surface receptor is activated through proteolytic cleavage of its extracellular amino terminus, resulting in a new amino terminus that acts as a tethered ligand that binds to an extracellular loop domain. Activation of the receptor has been shown to stimulate vascular smooth muscle relaxation, dilate blood vessels, increase blood flow, and lower blood pressure. This protein is also important in the inflammatory response, as well as innate and adaptive immunity. [provided by RefSeq, Jun 2016]

F2RL1 links:

ENSG00000289924 (HGNC:):

ENSG00000289924 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 5-76819186-C-A is Benign according to our data. Variant chr5-76819186-C-A is described in ClinVar as Benign. ClinVar VariationId is 789180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.209 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005242.6. 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
	F2RL1	NM_005242.6	MANE Select	c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 2	NP_005233.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F2RL1	ENST00000296677.5	TSL:1 MANE Select	c.4C>A	p.Arg2Arg	synonymous	Exon 1 of 2	ENSP00000296677.4	P55085
F2RL1	ENST00000514165.1	TSL:3	c.-201+185C>A		intron	N/A	ENSP00000425622.1	D6RJH3
ENSG00000289924	ENST00000701779.1		n.392G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.00556

AC:

846

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00939

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00558

AC:

1092

AN:

195644

AF XY:

0.00604

show subpopulations

Gnomad AFR exome

AF:

0.00212

Gnomad AMR exome

AF:

0.00566

Gnomad ASJ exome

AF:

0.00211

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.00795

Gnomad OTH exome

AF:

0.00791

GnomAD4 exome

AF:

0.00876

AC:

12517

AN:

1428850

Hom.:

Cov.:

AF XY:

0.00861

AC XY:

6110

AN XY:

709680

show subpopulations

African (AFR)

AF:

0.00129

AC:

AN:

33300

American (AMR)

AF:

0.00584

AC:

234

AN:

40068

Ashkenazi Jewish (ASJ)

AF:

0.00192

AC:

AN:

25574

East Asian (EAS)

AF:

0.0000257

AC:

AN:

38934

South Asian (SAS)

AF:

0.00431

AC:

358

AN:

83056

European-Finnish (FIN)

AF:

0.00147

AC:

AN:

38130

Middle Eastern (MID)

AF:

0.00111

AC:

AN:

5416

European-Non Finnish (NFE)

AF:

0.0101

AC:

11187

AN:

1104770

Other (OTH)

AF:

0.00978

AC:

583

AN:

59602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

574

1148

1722

2296

2870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152278

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

41564

American (AMR)

AF:

0.00653

AC:

100

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00228

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00940

AC:

639

AN:

68008

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

125

166

208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00734

Hom.:

Bravo

AF:

0.00588

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.1

(source)

DANN

Benign

0.63

PhyloP100

-0.21

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over