chr3-123980976-A-C

Position:

• chr3-123980976-A-C

Variant summary

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

The NM_001317774.2(ROPN1):​c.-12-483T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,218 control chromosomes in the GnomAD database, including 1,246 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 (1246 hom., cov: 32)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROPN1	NM_001317774.2	c.-12-483T>G		intron_variant		ENST00000405845.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROPN1	ENST00000405845.8	c.-12-483T>G		intron_variant		1	NM_001317774.2	P2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17298 AN: 152100 Hom.: 1244 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.114 AC: 17301 AN: 152218 Hom.: 1246 Cov.: 32 AF XY: 0.114 AC XY: 8502 AN XY: 74418

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.128

Alfa AF: 0.149 Hom.: 2405

Bravo AF: 0.107

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.60

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: rs17310770; hg19: chr3-123699823;