3-123977602-G-C

Position:

• chr3-123977602-G-C

Variant summary

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

The NM_001317774.2(ROPN1):​c.117-621C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,264 control chromosomes in the GnomAD database, including 1,226 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 0.11 (1226 hom., cov: 32)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

ROPN1 (HGNC:17692): (rhophilin associated tail protein 1) The protein encoded by this gene is found in the fibrous sheath of spermatazoa, where it interacts with rhophilin, a Rho GTPase binding protein. The encoded protein also can bind an A-kinase anchoring protein (AKAP110) and a calcium-binding tyrosine phosphorylation-regulated protein (CABYR). This protein may be involved in sperm motility and has been shown to be a cancer-testis antigen in hematologic malignancies. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROPN1	NM_001317774.2	c.117-621C>G		intron_variant		ENST00000405845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROPN1	ENST00000405845.8	c.117-621C>G		intron_variant		1	NM_001317774.2	P2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17120 AN: 152146 Hom.: 1224 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.112 AC: 17123 AN: 152264 Hom.: 1226 Cov.: 32 AF XY: 0.113 AC XY: 8414 AN XY: 74466

Gnomad4 AFR AF: 0.0311

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.127

Alfa AF: 0.126 Hom.: 174

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.69

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: rs17376453; hg19: chr3-123696449;