13-31758155-C-G

Variant names:

• chr13-31758155-C-G
• rs9548977
• NM_130806.5:c.95-103C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130806.5(RXFP2):​c.95-103C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 1,107,404 control chromosomes in the GnomAD database, including 4,014 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (528 hom., cov: 32)
  • Exomes 𝑓: 0.081 (3486 hom.)
• Consequence: RXFP2 NM_130806.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.626
• Publications: 4 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 13-31758155-C-G is Benign according to our data. Variant chr13-31758155-C-G is described in ClinVar as [Benign]. Clinvar id is 1239108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.95-103C>G		intron_variant	Intron 1 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.95-103C>G		intron_variant	Intron 1 of 16		NP_001159530.1
RXFP2	XM_017020389.2	c.95-103C>G		intron_variant	Intron 1 of 14		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.95-103C>G		intron_variant	Intron 1 of 17	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.95-103C>G		intron_variant	Intron 1 of 16	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12572 AN: 152046 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0872

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.0669

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0876

Gnomad OTH AF: 0.0938

GnomAD4 exome AF: 0.0814 AC: 77793 AN: 955240 Hom.: 3486 AF XY: 0.0820 AC XY: 40797 AN XY: 497816

African (AFR) AF: 0.0757 AC: 1792 AN: 23684

American (AMR) AF: 0.0557 AC: 2445 AN: 43918

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2728 AN: 22904

East Asian (EAS) AF: 0.0832 AC: 3098 AN: 37220

South Asian (SAS) AF: 0.0764 AC: 5757 AN: 75330

European-Finnish (FIN) AF: 0.0800 AC: 3903 AN: 48810

Middle Eastern (MID) AF: 0.114 AC: 549 AN: 4836

European-Non Finnish (NFE) AF: 0.0820 AC: 53664 AN: 654654

Other (OTH) AF: 0.0879 AC: 3857 AN: 43884

GnomAD4 genome AF: 0.0826 AC: 12570 AN: 152164 Hom.: 528 Cov.: 32 AF XY: 0.0821 AC XY: 6105 AN XY: 74392

African (AFR) AF: 0.0744 AC: 3087 AN: 41514

American (AMR) AF: 0.0872 AC: 1333 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 448 AN: 3472

East Asian (EAS) AF: 0.0822 AC: 426 AN: 5184

South Asian (SAS) AF: 0.0682 AC: 328 AN: 4808

European-Finnish (FIN) AF: 0.0669 AC: 710 AN: 10606

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.0876 AC: 5952 AN: 67974

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0895 Hom.: 90

Bravo AF: 0.0814

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 20, 2021

GeneDx

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	-0.82
CADD	Benign	0.96
DANN	Benign	0.36
PhyloP100		-0.63
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs9548977; hg19: chr13-32332292; COSMIC: COSV53639916;