5-76833228-T-C

Position:

• chr5-76833228-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005242.6(F2RL1):​c.621T>C​(p.Ile207Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 1,613,900 control chromosomes in the GnomAD database, including 718,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (68872 hom., cov: 28)
  • Exomes 𝑓: 0.94 (649166 hom.)
• Consequence: F2RL1 NM_005242.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.323 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2RL1	NM_005242.6	c.621T>C	p.Ile207Ile	synonymous_variant	2/2	ENST00000296677.5	NP_005233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2RL1	ENST00000296677.5	c.621T>C	p.Ile207Ile	synonymous_variant	2/2	1	NM_005242.6	ENSP00000296677.4
F2RL1	ENST00000514165.1	c.*1T>C		downstream_gene_variant		3		ENSP00000425622.1

Frequencies

GnomAD3 genomes AF: 0.948 AC: 144073 AN: 151926 Hom.: 68817 Cov.: 28

Gnomad AFR AF: 0.989

Gnomad AMI AF: 0.992

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.980

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.950

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.945

GnomAD3 exomes AF: 0.919 AC: 230955 AN: 251178 Hom.: 107883 AF XY: 0.922 AC XY: 125217 AN XY: 135746

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.927

Gnomad ASJ exome AF: 0.980

Gnomad EAS exome AF: 0.515

Gnomad SAS exome AF: 0.953

Gnomad FIN exome AF: 0.936

Gnomad NFE exome AF: 0.954

Gnomad OTH exome AF: 0.938

GnomAD4 exome AF: 0.940 AC: 1373649 AN: 1461856 Hom.: 649166 Cov.: 71 AF XY: 0.940 AC XY: 683830 AN XY: 727222

Gnomad4 AFR exome AF: 0.992

Gnomad4 AMR exome AF: 0.929

Gnomad4 ASJ exome AF: 0.979

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.952

Gnomad4 FIN exome AF: 0.938

Gnomad4 NFE exome AF: 0.952

Gnomad4 OTH exome AF: 0.932

GnomAD4 genome AF: 0.948 AC: 144191 AN: 152044 Hom.: 68872 Cov.: 28 AF XY: 0.945 AC XY: 70195 AN XY: 74286

Gnomad4 AFR AF: 0.989

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.980

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.949

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.954

Gnomad4 OTH AF: 0.945

Alfa AF: 0.954 Hom.: 107911

Bravo AF: 0.946

Asia WGS AF: 0.802 AC: 2793 AN: 3478

EpiCase AF: 0.959

EpiControl AF: 0.957

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.1
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs631465; hg19: chr5-76129053; COSMIC: COSV56995235; COSMIC: COSV56995235;