rs814597

chr5-10468817-C-T

Variant summary

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

The XM_006714504.4(ROPN1L):c.593+7458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,082 control chromosomes in the GnomAD database, including 3,712 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 0.18 (3712 hom., cov: 33)
• Consequence: ROPN1L XM_006714504.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ROPN1L	XM_006714504.4	c.593+7458C>T		intron_variant
ROPN1L	XM_017009946.3	c.594-2993C>T		intron_variant
ROPN1L	XM_017009947.3	c.593+7458C>T		intron_variant
ROPN1L	XM_047417808.1	c.594-2993C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ROPN1L	ENST00000510520.5	n.886-2993C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27708 AN: 151966 Hom.: 3687 Cov.: 33

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.183 AC: 27771 AN: 152082 Hom.: 3712 Cov.: 33 AF XY: 0.190 AC XY: 14153 AN XY: 74330

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.180

Alfa AF: 0.137 Hom.: 1075

Bravo AF: 0.200

Asia WGS AF: 0.504 AC: 1749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.73
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs814597; hg19: chr5-10468929;