chr3-123977602-G-C

Variant names:

• chr3-123977602-G-C
• rs17376453
• NM_001317774.2:c.117-621C>G

Variant summary

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

The NM_001317774.2(ROPN1):​c.117-621C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,264 control chromosomes in the GnomAD database, including 1,226 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 0.11 (1226 hom., cov: 32)
• Consequence: ROPN1 NM_001317774.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROPN1	NM_001317774.2	c.117-621C>G		intron_variant	Intron 2 of 5	ENST00000405845.8	NP_001304703.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1	ENST00000405845.8	c.117-621C>G		intron_variant	Intron 2 of 5	1	NM_001317774.2	ENSP00000385919.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17120 AN: 152146 Hom.: 1224 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.112 AC: 17123 AN: 152264 Hom.: 1226 Cov.: 32 AF XY: 0.113 AC XY: 8414 AN XY: 74466

African (AFR) AF: 0.0311 AC: 1295 AN: 41576

American (AMR) AF: 0.104 AC: 1585 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.104 AC: 541 AN: 5180

South Asian (SAS) AF: 0.203 AC: 978 AN: 4818

European-Finnish (FIN) AF: 0.129 AC: 1365 AN: 10600

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10351 AN: 68002

Other (OTH) AF: 0.127 AC: 268 AN: 2110

Alfa AF: 0.126 Hom.: 174

Bravo AF: 0.106

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.69
PhyloP100		-1.2
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: rs17376453; hg19: chr3-123696449;