rs12327666

Positions:

• chr19-14029109-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080864.4(RLN3):​c.190+715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 152,078 control chromosomes in the GnomAD database, including 367 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 0.065 (367 hom., cov: 31)
• Consequence: RLN3 NM_080864.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

Genes affected

RLN3 (HGNC:17135): (relaxin 3) This gene encodes a member of the relaxin family of insulin-like hormones that is expressed predominantly in the brain and plays a role in physiological processes such as stress, memory and appetite regulation. The encoded protein is a precursor that is proteolytically processed to generate a heterodimeric mature form consisting A and B chains interlinked by disulfide bonds. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLN3	NM_080864.4	c.190+715G>A		intron_variant		ENST00000431365.3	NP_543140.1
RLN3	NM_001311197.2	c.190+715G>A		intron_variant			NP_001298126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLN3	ENST00000431365.3	c.190+715G>A		intron_variant		1	NM_080864.4	ENSP00000397415.2
RLN3	ENST00000585987.1	c.190+715G>A		intron_variant		1		ENSP00000467130.1

Frequencies

GnomAD3 genomes AF: 0.0652 AC: 9901 AN: 151960 Hom.: 368 Cov.: 31

Gnomad AFR AF: 0.0958

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.0531

Gnomad SAS AF: 0.0794

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0561

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

GnomAD4 genome AF: 0.0652 AC: 9915 AN: 152078 Hom.: 367 Cov.: 31 AF XY: 0.0656 AC XY: 4876 AN XY: 74336

Gnomad4 AFR AF: 0.0960

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0616

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.0790

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.0548

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0548 Hom.: 232

Bravo AF: 0.0639

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs12327666; hg19: chr19-14139921;