chr5-10463995-C-T

Variant names:

• chr5-10463995-C-T
• rs2967951
• NM_031916.5:c.594-853C>T

Variant summary

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

The NM_031916.5(ROPN1L):​c.594-853C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,144 control chromosomes in the GnomAD database, including 4,011 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 0.19 (4011 hom., cov: 33)
• Consequence: ROPN1L NM_031916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11
• Publications: 21 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]

LOC124900940 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ROPN1L	NM_031916.5	c.594-853C>T		intron_variant	Intron 4 of 4	ENST00000274134.5	NP_114122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ROPN1L	ENST00000274134.5	c.594-853C>T		intron_variant	Intron 4 of 4	1	NM_031916.5	ENSP00000274134.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29226 AN: 152026 Hom.: 3987 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.193 AC: 29295 AN: 152144 Hom.: 4011 Cov.: 33 AF XY: 0.200 AC XY: 14867 AN XY: 74388

African (AFR) AF: 0.245 AC: 10188 AN: 41506

American (AMR) AF: 0.309 AC: 4717 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3472

East Asian (EAS) AF: 0.660 AC: 3388 AN: 5130

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4822

European-Finnish (FIN) AF: 0.112 AC: 1194 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7234 AN: 67994

Other (OTH) AF: 0.189 AC: 399 AN: 2114

Alfa AF: 0.145 Hom.: 8223

Bravo AF: 0.212

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-2.1
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: rs2967951; hg19: chr5-10464107;