Genetic Variant RXFP2:c.241+15C>T (chr13-31758419-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_130806.5(RXFP2):c.241+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,613,246 control chromosomes in the GnomAD database, including 25,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2478 hom., cov: 32)

Exomes 𝑓: 0.18 ( 23088 hom. )

Consequence

RXFP2
NM_130806.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.377

Publications

7 publications found

Variant links:

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

RXFP2 Gene-Disease associations (from GenCC):

cryptorchidism
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
disorder of sexual differentiation
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

RXFP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-31758419-C-T is Benign according to our data. Variant chr13-31758419-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130806.5. 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
	RXFP2	NM_130806.5	MANE Select	c.241+15C>T		intron	N/A	NP_570718.1	Q8WXD0-1
	RXFP2	NM_001166058.2		c.241+15C>T		intron	N/A	NP_001159530.1	Q8WXD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP2	ENST00000298386.7	TSL:1 MANE Select	c.241+15C>T		intron	N/A	ENSP00000298386.2	Q8WXD0-1
	RXFP2	ENST00000380314.2	TSL:1	c.241+15C>T		intron	N/A	ENSP00000369670.1	Q8WXD0-2

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27725

AN:

151912

Hom.:

2478

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.237

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.229

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.189

AC:

47577

AN:

251180

AF XY:

0.192

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.242

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.200

GnomAD4 exome

AF:

0.175

AC:

256090

AN:

1461212

Hom.:

23088

Cov.:

AF XY:

0.177

AC XY:

128779

AN XY:

726922

show subpopulations

African (AFR)

AF:

0.173

AC:

5798

AN:

33462

American (AMR)

AF:

0.180

AC:

8035

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5629

AN:

26126

East Asian (EAS)

AF:

0.235

AC:

9344

AN:

39686

South Asian (SAS)

AF:

0.219

AC:

18871

AN:

86238

European-Finnish (FIN)

AF:

0.200

AC:

10693

AN:

53380

Middle Eastern (MID)

AF:

0.232

AC:

1336

AN:

5750

European-Non Finnish (NFE)

AF:

0.167

AC:

185432

AN:

1111500

Other (OTH)

AF:

0.181

AC:

10952

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

10629

21258

31888

42517

53146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6636

13272

19908

26544

33180

<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:

0.182

AC:

27742

AN:

152034

Hom.:

2478

Cov.:

AF XY:

0.184

AC XY:

13657

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.179

AC:

7410

AN:

41468

American (AMR)

AF:

0.171

AC:

2615

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

760

AN:

3472

East Asian (EAS)

AF:

0.227

AC:

1170

AN:

5158

South Asian (SAS)

AF:

0.237

AC:

1143

AN:

4826

European-Finnish (FIN)

AF:

0.204

AC:

2150

AN:

10562

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.173

AC:

11762

AN:

67956

Other (OTH)

AF:

0.192

AC:

405

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1148

2296

3444

4592

5740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.178

Hom.:

475

Bravo

AF:

0.181

Asia WGS

AF:

0.237

AC:

824

AN:

3478

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

-0.86

CADD

Benign

0.70

(source)

DANN

Benign

0.52

PhyloP100

-0.38

Mutation Taster

=100/0

polymorphism (auto)

(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