1-155942290-G-A

Variant names:

• chr1-155942290-G-A
• rs202002819
• NM_181885.3:c.581G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_181885.3(RXFP4):​c.581G>A​(p.Arg194His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,600,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R194C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: RXFP4 NM_181885.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03
• Publications: 1 publications found

Genes affected

RXFP4 (HGNC:14666): (relaxin family peptide/INSL5 receptor 4) GPR100 is a member of the rhodopsin family of G protein-coupled receptors (GPRs) (Fredriksson et al., 2003 [PubMed 14623098]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.25778502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181885.3. 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
	RXFP4	NM_181885.3	MANE Select	c.581G>A	p.Arg194His	missense	Exon 1 of 1	NP_871001.1	Q8TDU9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP4	ENST00000368318.5	TSL:6 MANE Select	c.581G>A	p.Arg194His	missense	Exon 1 of 1	ENSP00000357301.4	Q8TDU9

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000742 AC: 18 AN: 242550 AF XY: 0.0000535

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000297

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000332

Gnomad NFE exome AF: 0.0000458

Gnomad OTH exome AF: 0.000681

GnomAD4 exome AF: 0.0000400 AC: 58 AN: 1448538 Hom.: 0 Cov.: 32 AF XY: 0.0000334 AC XY: 24 AN XY: 718638

African (AFR) AF: 0.000240 AC: 8 AN: 33284

American (AMR) AF: 0.000137 AC: 6 AN: 43874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25290

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39478

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84950

European-Finnish (FIN) AF: 0.000321 AC: 17 AN: 52970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.0000208 AC: 23 AN: 1103284

Other (OTH) AF: 0.0000335 AC: 2 AN: 59706

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74364

African (AFR) AF: 0.0000965 AC: 4 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5196

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000783 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.11
Eigen_PC	Benign	-0.0044
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.14
Sift	Benign	0.046	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.65		Loss of MoRF binding (P = 0.0165)
MVP		0.43
MPC		0.54
ClinPred		0.43	T
GERP RS		2.9
Varity_R		0.096
gMVP		0.45
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs202002819; hg19: chr1-155912081;