Variant 5-76819186-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2RL1	NM_005242.6 link	c.4C>A	p.Arg2Arg	synonymous_variant	Exon 1 of 2	ENST00000296677.5	NP_005233.4	P55085

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
F2RL1	ENST00000296677.5 link	c.4C>A	p.Arg2Arg	synonymous_variant	Exon 1 of 2	1	NM_005242.6	ENSP00000296677.4	P55085
F2RL1	ENST00000514165.1 link	c.-201+185C>A		intron_variant	Intron 1 of 1	3		ENSP00000425622.1	D6RJH3
ENSG00000289924	ENST00000701779.1 link	n.392G>T		non_coding_transcript_exon_variant	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

GnomAD3 exomes

AF:

0.00558

AC:

1092

AN:

195644

Hom.:

AF XY:

0.00604

AC XY:

655

AN XY:

108474

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 SAS exome

AF:

0.00434

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

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00584

Gnomad4 ASJ exome

AF:

0.00192

Gnomad4 EAS exome

AF:

0.0000257

Gnomad4 SAS exome

AF:

0.00431

Gnomad4 FIN exome

AF:

0.00147

Gnomad4 NFE exome

AF:

0.0101

Gnomad4 OTH exome

AF:

0.00978

GnomAD4 genome

AF:

0.00556

AC:

846

AN:

152278

Hom.:

Cov.:

AF XY:

0.00529

AC XY:

394

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00168

Gnomad4 AMR

AF:

0.00653

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00940

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00734

Hom.:

Bravo

AF:

0.00588

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.1

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over