chr19-14028192-A-T

Variant names:

• chr19-14028192-A-T
• rs1982632
• NM_080864.4:c.-13A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080864.4(RLN3):​c.-13A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,403,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RLN3 NM_080864.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 23 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN3	NM_080864.4	c.-13A>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000431365.3	NP_543140.1
RLN3	NM_001311197.2	c.-13A>T		5_prime_UTR_variant	Exon 1 of 3		NP_001298126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLN3	ENST00000431365.3	c.-13A>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_080864.4	ENSP00000397415.2
RLN3	ENST00000585987.1	c.-13A>T		upstream_gene_variant		1		ENSP00000467130.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000961 AC: 2 AN: 208174 AF XY: 0.0000179

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000755

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1403490 Hom.: 0 Cov.: 31 AF XY: 0.00000289 AC XY: 2 AN XY: 693032

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.0000561 AC: 2 AN: 35630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22324

East Asian (EAS) AF: 0.00 AC: 0 AN: 38756

South Asian (SAS) AF: 0.00 AC: 0 AN: 78008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082606

Other (OTH) AF: 0.00 AC: 0 AN: 57684

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.44
PhyloP100		-0.53
PromoterAI		0.017	Neutral

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: rs1982632; hg19: chr19-14139004;