rs1092913

chr5-10467590-G-A

Variant summary

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

The XM_006714504.4(ROPN1L):c.593+6231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,142 control chromosomes in the GnomAD database, including 4,170 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 0.20 (4170 hom., cov: 33)
• Consequence: ROPN1L XM_006714504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.505

Genes affected

ROPN1L (HGNC:24060): (rhophilin associated tail protein 1 like) This gene encodes a member of the ropporin family. The encoded protein is present in sperm and interacts with A-kinase anchoring protein, AKAP3, through the amphipathic helix region of AKAP3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2014]

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 (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROPN1L	XM_006714504.4	c.593+6231G>A		intron_variant
ROPN1L	XM_017009946.3	c.594-4220G>A		intron_variant
ROPN1L	XM_017009947.3	c.593+6231G>A		intron_variant
ROPN1L	XM_047417808.1	c.594-4220G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROPN1L	ENST00000510520.5	n.886-4220G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29854 AN: 152024 Hom.: 4145 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.197 AC: 29932 AN: 152142 Hom.: 4170 Cov.: 33 AF XY: 0.204 AC XY: 15172 AN XY: 74364

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.193

Alfa AF: 0.145 Hom.: 3824

Bravo AF: 0.217

Asia WGS AF: 0.509 AC: 1766 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	1.0
Dann	Benign	0.27

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1092913; hg19: chr5-10467702; COSMIC: COSV56873062;