5-178145926-C-T

Position:

• chr5-178145926-C-T

Variant summary

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

The NM_022762.5(RMND5B):​c.695-188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 571,876 control chromosomes in the GnomAD database, including 160,388 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 0.73 (41122 hom., cov: 34)
  • Exomes 𝑓: 0.75 (119266 hom.)
• Consequence: RMND5B NM_022762.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.235

Genes affected

RMND5B (HGNC:26181): (required for meiotic nuclear division 5 homolog B) Predicted to enable metal ion binding activity and ubiquitin protein ligase activity. Predicted to contribute to ubiquitin-protein transferase activity. Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMND5B	NM_022762.5	c.695-188C>T		intron_variant		ENST00000313386.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMND5B	ENST00000313386.9	c.695-188C>T		intron_variant		1	NM_022762.5	P1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111486 AN: 152078 Hom.: 41103 Cov.: 34

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.727

GnomAD4 exome AF: 0.752 AC: 315586 AN: 419680 Hom.: 119266 Cov.: 4 AF XY: 0.752 AC XY: 163922 AN XY: 217900

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.830

Gnomad4 ASJ exome AF: 0.679

Gnomad4 EAS exome AF: 0.703

Gnomad4 SAS exome AF: 0.753

Gnomad4 FIN exome AF: 0.797

Gnomad4 NFE exome AF: 0.756

Gnomad4 OTH exome AF: 0.741

GnomAD4 genome AF: 0.733 AC: 111564 AN: 152196 Hom.: 41122 Cov.: 34 AF XY: 0.735 AC XY: 54706 AN XY: 74412

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.811

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.727

Alfa AF: 0.753 Hom.: 22981

Bravo AF: 0.727

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.71

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: rs6873523; hg19: chr5-177572927;