rs6810298

Positions:

• chr3-123976128-G-A
• chr3-123976128-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.235-588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 152,028 control chromosomes in the GnomAD database, including 24,335 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 0.54 (24335 hom., cov: 31)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138

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]

ROPN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROPN1	NM_001317774.2	c.235-588C>T		intron_variant		ENST00000405845.8	NP_001304703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROPN1	ENST00000405845.8	c.235-588C>T		intron_variant		1	NM_001317774.2	ENSP00000385919.3

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81597 AN: 151910 Hom.: 24334 Cov.: 31

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.537 AC: 81614 AN: 152028 Hom.: 24335 Cov.: 31 AF XY: 0.528 AC XY: 39245 AN XY: 74298

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.566

Alfa AF: 0.635 Hom.: 6281

Bravo AF: 0.515

Asia WGS AF: 0.305 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.59

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: rs6810298; hg19: chr3-123694975;