5-178145926-C-T

Variant names:

• chr5-178145926-C-T
• rs6873523
• NM_022762.5:c.695-188C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022762.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMND5B	NM_022762.5	MANE Select	c.695-188C>T		intron	N/A	NP_073599.2
	RMND5B	NM_001288794.2		c.695-188C>T		intron	N/A	NP_001275723.1
	RMND5B	NM_001288795.2		c.656-188C>T		intron	N/A	NP_001275724.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RMND5B	ENST00000313386.9	TSL:1 MANE Select	c.695-188C>T		intron	N/A	ENSP00000320623.4
	RMND5B	ENST00000940697.1		c.857-188C>T		intron	N/A	ENSP00000610756.1
	RMND5B	ENST00000940698.1		c.857-188C>T		intron	N/A	ENSP00000610757.1

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

African (AFR) AF: 0.661 AC: 8087 AN: 12240

American (AMR) AF: 0.830 AC: 14916 AN: 17978

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 8693 AN: 12804

East Asian (EAS) AF: 0.703 AC: 21452 AN: 30514

South Asian (SAS) AF: 0.753 AC: 27317 AN: 36270

European-Finnish (FIN) AF: 0.797 AC: 22478 AN: 28202

Middle Eastern (MID) AF: 0.775 AC: 1402 AN: 1808

European-Non Finnish (NFE) AF: 0.756 AC: 193031 AN: 255274

Other (OTH) AF: 0.741 AC: 18210 AN: 24590

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

African (AFR) AF: 0.658 AC: 27281 AN: 41490

American (AMR) AF: 0.795 AC: 12153 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2365 AN: 3468

East Asian (EAS) AF: 0.705 AC: 3652 AN: 5178

South Asian (SAS) AF: 0.759 AC: 3664 AN: 4830

European-Finnish (FIN) AF: 0.811 AC: 8604 AN: 10612

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51462 AN: 68006

Other (OTH) AF: 0.727 AC: 1534 AN: 2110

Alfa AF: 0.752 Hom.: 31311

Bravo AF: 0.727

Asia WGS AF: 0.725 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		-0.23
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: rs6873523; hg19: chr5-177572927;