5-10460261-G-C

Variant names:

• chr5-10460261-G-C
• rs1809880
• NM_031916.5:c.418-923G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031916.5(ROPN1L):​c.418-923G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,296 control chromosomes in the GnomAD database, including 58,234 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 0.87 (58234 hom., cov: 35)
• Consequence: ROPN1L NM_031916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031916.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1L	NM_031916.5	MANE Select	c.418-923G>C		intron	N/A	NP_114122.2
	ROPN1L	NM_001201466.2		c.418-923G>C		intron	N/A	NP_001188395.1	Q96C74

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROPN1L	ENST00000274134.5	TSL:1 MANE Select	c.418-923G>C		intron	N/A	ENSP00000274134.4	Q96C74
	ROPN1L	ENST00000503804.5	TSL:2	c.418-923G>C		intron	N/A	ENSP00000421405.1	Q96C74
	ROPN1L	ENST00000510520.5	TSL:3	n.710-923G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132472 AN: 152178 Hom.: 58209 Cov.: 35

Gnomad AFR AF: 0.732

Gnomad AMI AF: 0.905

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.968

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.870 AC: 132554 AN: 152296 Hom.: 58234 Cov.: 35 AF XY: 0.875 AC XY: 65159 AN XY: 74474

African (AFR) AF: 0.732 AC: 30395 AN: 41536

American (AMR) AF: 0.908 AC: 13910 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3123 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5173 AN: 5178

South Asian (SAS) AF: 0.968 AC: 4678 AN: 4834

European-Finnish (FIN) AF: 0.945 AC: 10033 AN: 10620

Middle Eastern (MID) AF: 0.864 AC: 254 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62278 AN: 68024

Other (OTH) AF: 0.892 AC: 1885 AN: 2114

Alfa AF: 0.892 Hom.: 7110

Bravo AF: 0.860

Asia WGS AF: 0.964 AC: 3352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.50
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1809880; hg19: chr5-10460373;