Genetic Variant NM_016568.3:c.-466A>G (chr5-33936275-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_016568.3(RXFP3):c.-466A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 155,824 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 72 hom., cov: 33)

Exomes 𝑓: 0.035 ( 6 hom. )

Consequence

RXFP3
NM_016568.3 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.261

Publications

1 publications found

Variant links:

Genes affected

RXFP3 (HGNC:24883): (relaxin family peptide receptor 3) Predicted to enable G protein-coupled peptide receptor activity. Involved in positive regulation of cytokinesis. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RXFP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0258 (3926/152338) while in subpopulation NFE AF = 0.0367 (2497/68022). AF 95% confidence interval is 0.0355. There are 72 homozygotes in GnomAd4. There are 1931 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 72 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016568.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP3	NM_016568.3	MANE Select	c.-466A>G		upstream_gene	N/A	NP_057652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RXFP3	ENST00000330120.5	TSL:6 MANE Select	c.-466A>G		upstream_gene	N/A	ENSP00000328708.3

Frequencies

GnomAD3 genomes

AF:

0.0258

AC:

3928

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00617

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.0331

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0568

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0234

GnomAD4 exome

AF:

0.0350

AC:

122

AN:

3486

Hom.:

AF XY:

0.0365

AC XY:

AN XY:

1752

show subpopulations

African (AFR)

AF:

0.0130

AC:

AN:

154

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0543

AC:

AN:

184

East Asian (EAS)

AF:

0.00

AC:

AN:

112

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0818

AC:

AN:

110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0365

AC:

AN:

2578

Other (OTH)

AF:

0.0318

AC:

AN:

220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0258

AC:

3926

AN:

152338

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1931

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00616

AC:

256

AN:

41586

American (AMR)

AF:

0.0197

AC:

301

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0331

AC:

115

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00228

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0568

AC:

603

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0367

AC:

2497

AN:

68022

Other (OTH)

AF:

0.0232

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

214

429

643

858

1072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0327

Hom.:

Bravo

AF:

0.0232

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.2

(source)

DANN

Benign

0.41

PhyloP100

-0.26

PromoterAI

0.020

Neutral

(source)

Splicing

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