9-5339635-C-A

Variant names:

• chr9-5339635-C-A
• rs200387461
• NM_006911.4:c.112G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006911.4(RLN1):​c.112G>T​(p.Glu38*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RLN1 NM_006911.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

Genes affected

RLN1 (HGNC:10026): (relaxin 1) Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In humans there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3, where RLN1 and RLN2 share high sequence homology. The protein encoded by this gene is synthesized as a single-chain polypeptide but the active form consists of an A chain and a B chain linked by disulfide bonds. Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility, regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN1	NM_006911.4	c.112G>T	p.Glu38*	stop_gained	Exon 1 of 2	ENST00000223862.2	NP_008842.1
RLN1	XM_047423703.1	c.112G>T	p.Glu38*	stop_gained	Exon 1 of 3		XP_047279659.1
RLN1	XM_047423706.1	c.-48+1186G>T		intron_variant	Intron 1 of 1		XP_047279662.1
RLN1	XM_047423705.1	c.-320G>T		upstream_gene_variant			XP_047279661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLN1	ENST00000223862.2	c.112G>T	p.Glu38*	stop_gained	Exon 1 of 2	1	NM_006911.4	ENSP00000223862.1
RLN1	ENST00000487557.2	n.-239G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461656 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	29
DANN	Uncertain	0.98
Eigen	Benign	-0.023
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.054	N
Vest4		0.56
GERP RS		1.9

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: rs200387461; hg19: chr9-5339635;