rs764553245

Variant names:

• chr9-5339673-G-C
• NM_006911.4:c.74C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-5339673-G-C
• chr9-5339673-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006911.4(RLN1):​c.74C>G​(p.Ala25Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 27)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: RLN1 NM_006911.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06532666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN1	NM_006911.4	c.74C>G	p.Ala25Gly	missense_variant	Exon 1 of 2	ENST00000223862.2	NP_008842.1
RLN1	XM_047423703.1	c.74C>G	p.Ala25Gly	missense_variant	Exon 1 of 3		XP_047279659.1
RLN1	XM_047423706.1	c.-48+1148C>G		intron_variant	Intron 1 of 1		XP_047279662.1
RLN1	XM_047423705.1	c.-358C>G		upstream_gene_variant			XP_047279661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLN1	ENST00000223862.2	c.74C>G	p.Ala25Gly	missense_variant	Exon 1 of 2	1	NM_006911.4	ENSP00000223862.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460988 Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6 AN XY: 726800

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: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.43
DANN	Benign	0.22
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.0090
Sift	Benign	0.39	T
Sift4G	Benign	0.34	T
Polyphen		0.052	B
Vest4		0.049
MutPred		0.30		Loss of stability (P = 0.0343);
MVP		0.048
MPC		0.075
ClinPred		0.23	T
GERP RS		-1.9
Varity_R		0.034
gMVP		0.070

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5339673;