5-76833228-T-C

Variant names:

• chr5-76833228-T-C
• rs631465
• NM_005242.6:c.621T>C

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
F2RL1	NM_005242.6	c.621T>C	p.Ile207Ile	synonymous_variant	Exon 2 of 2	ENST00000296677.5	NP_005233.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F2RL1	ENST00000296677.5	c.621T>C	p.Ile207Ile	synonymous_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.919 AC: 230955 AN: 251178 AF XY: 0.922

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 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 AC: 33216 AN: 33480

Gnomad4 AMR exome AF: 0.929 AC: 41558 AN: 44724

Gnomad4 ASJ exome AF: 0.979 AC: 25595 AN: 26136

Gnomad4 EAS exome AF: 0.530 AC: 21035 AN: 39698

Gnomad4 SAS exome AF: 0.952 AC: 82106 AN: 86258

Gnomad4 FIN exome AF: 0.938 AC: 50090 AN: 53418

Gnomad4 NFE exome AF: 0.952 AC: 1058056 AN: 1111980

Gnomad4 Remaining exome AF: 0.932 AC: 56306 AN: 60394

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 AC: 0.988769 AN: 0.988769

Gnomad4 AMR AF: 0.950 AC: 0.949621 AN: 0.949621

Gnomad4 ASJ AF: 0.980 AC: 0.979551 AN: 0.979551

Gnomad4 EAS AF: 0.521 AC: 0.521185 AN: 0.521185

Gnomad4 SAS AF: 0.949 AC: 0.949396 AN: 0.949396

Gnomad4 FIN AF: 0.941 AC: 0.940514 AN: 0.940514

Gnomad4 NFE AF: 0.954 AC: 0.954282 AN: 0.954282

Gnomad4 OTH AF: 0.945 AC: 0.945076 AN: 0.945076

Alfa AF: 0.955 Hom.: 132112

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
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

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