rs2278354

Positions:

• chr5-10448866-C-A

Variant summary

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

The NM_031916.5(ROPN1L):​c.255+483C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,100 control chromosomes in the GnomAD database, including 41,624 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 0.71 (41624 hom., cov: 33)
• Consequence: ROPN1L NM_031916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ROPN1L	NM_031916.5	c.255+483C>A		intron_variant		ENST00000274134.5	NP_114122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ROPN1L	ENST00000274134.5	c.255+483C>A		intron_variant		1	NM_031916.5	ENSP00000274134	P1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107555 AN: 151982 Hom.: 41635 Cov.: 33

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.707 AC: 107553 AN: 152100 Hom.: 41624 Cov.: 33 AF XY: 0.703 AC XY: 52280 AN XY: 74340

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.649

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.732

Alfa AF: 0.791 Hom.: 6205

Bravo AF: 0.673

Asia WGS AF: 0.460 AC: 1603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.90

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: rs2278354; hg19: chr5-10448978;