chr13-31757975-T-C

Variant names:

• chr13-31757975-T-C
• rs9532456
• NM_130806.5:c.95-283T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130806.5(RXFP2):​c.95-283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 152,266 control chromosomes in the GnomAD database, including 75,784 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 1.0 (75784 hom., cov: 31)
• Consequence: RXFP2 NM_130806.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.25
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 13-31757975-T-C is Benign according to our data. Variant chr13-31757975-T-C is described in ClinVar as [Benign]. Clinvar id is 1257281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.95-283T>C		intron_variant	Intron 1 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.95-283T>C		intron_variant	Intron 1 of 16		NP_001159530.1
RXFP2	XM_017020389.2	c.95-283T>C		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.95-283T>C		intron_variant	Intron 1 of 17	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.95-283T>C		intron_variant	Intron 1 of 16	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.998 AC: 151799 AN: 152148 Hom.: 75725 Cov.: 31

Gnomad AFR AF: 0.992

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.999

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.998

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.998 AC: 151917 AN: 152266 Hom.: 75784 Cov.: 31 AF XY: 0.998 AC XY: 74290 AN XY: 74458

African (AFR) AF: 0.992 AC: 41207 AN: 41542

American (AMR) AF: 0.999 AC: 15286 AN: 15294

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4820 AN: 4820

European-Finnish (FIN) AF: 1.00 AC: 10604 AN: 10604

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68031 AN: 68032

Other (OTH) AF: 0.998 AC: 2105 AN: 2110

Alfa AF: 0.999 Hom.: 8645

Bravo AF: 0.997

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 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	-1.0
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-1.2
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: rs9532456; hg19: chr13-32332112;