13-31761703-A-T

Variant names:

• chr13-31761703-A-T
• rs9532478
• NM_130806.5:c.242-21A>T

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.242-21A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,550,826 control chromosomes in the GnomAD database, including 24,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2345 hom., cov: 33)
  • Exomes 𝑓: 0.18 (22461 hom.)
• Consequence: RXFP2 NM_130806.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.428
• Publications: 7 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=-0.78).
• BP6: Variant 13-31761703-A-T is Benign according to our data. Variant chr13-31761703-A-T is described in ClinVar as [Benign]. Clinvar id is 1268067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.242-21A>T		intron_variant	Intron 2 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.242-21A>T		intron_variant	Intron 2 of 16		NP_001159530.1
RXFP2	XM_017020389.2	c.242-21A>T		intron_variant	Intron 2 of 14		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.242-21A>T		intron_variant	Intron 2 of 17	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.242-21A>T		intron_variant	Intron 2 of 16	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26875 AN: 152080 Hom.: 2346 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.188 AC: 47127 AN: 250900 AF XY: 0.191

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.241

Gnomad FIN exome AF: 0.194

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.199

GnomAD4 exome AF: 0.177 AC: 246878 AN: 1398628 Hom.: 22461 Cov.: 22 AF XY: 0.178 AC XY: 124752 AN XY: 699598

African (AFR) AF: 0.154 AC: 4971 AN: 32332

American (AMR) AF: 0.178 AC: 7946 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5536 AN: 25616

East Asian (EAS) AF: 0.236 AC: 9258 AN: 39276

South Asian (SAS) AF: 0.219 AC: 18593 AN: 84946

European-Finnish (FIN) AF: 0.200 AC: 10658 AN: 53246

Middle Eastern (MID) AF: 0.233 AC: 1316 AN: 5660

European-Non Finnish (NFE) AF: 0.169 AC: 178054 AN: 1054796

Other (OTH) AF: 0.181 AC: 10546 AN: 58168

GnomAD4 genome AF: 0.177 AC: 26877 AN: 152198 Hom.: 2345 Cov.: 33 AF XY: 0.178 AC XY: 13234 AN XY: 74406

African (AFR) AF: 0.159 AC: 6587 AN: 41524

American (AMR) AF: 0.168 AC: 2575 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 758 AN: 3472

East Asian (EAS) AF: 0.227 AC: 1176 AN: 5184

South Asian (SAS) AF: 0.236 AC: 1138 AN: 4826

European-Finnish (FIN) AF: 0.204 AC: 2155 AN: 10586

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11765 AN: 67998

Other (OTH) AF: 0.187 AC: 396 AN: 2114

Alfa AF: 0.175 Hom.: 450

Bravo AF: 0.175

Asia WGS AF: 0.233 AC: 807 AN: 3476

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

- -

Nov 12, 2018

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	-0.78
CADD	Benign	0.18
DANN	Benign	0.81
PhyloP100		-0.43
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: rs9532478; hg19: chr13-32335840; COSMIC: COSV53633160;