rs6601217

chr5-178141838-G-Achr5-178141838-G-C

Variant summary

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

The NM_022762.5(RMND5B):c.140-745G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,140 control chromosomes in the GnomAD database, including 43,538 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 0.75 (43538 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: RMND5B NM_022762.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RMND5B	NM_022762.5	c.140-745G>A		intron_variant		ENST00000313386.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RMND5B	ENST00000313386.9	c.140-745G>A		intron_variant		1	NM_022762.5	P1

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114721 AN: 152020 Hom.: 43515 Cov.: 32

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.822

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.755 AC: 114802 AN: 152138 Hom.: 43538 Cov.: 32 AF XY: 0.757 AC XY: 56284 AN XY: 74388

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.784

Gnomad4 FIN AF: 0.822

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.753

Alfa AF: 0.729 Hom.: 2294

Bravo AF: 0.749

Asia WGS AF: 0.758 AC: 2632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.58
Dann	Benign	0.35

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: rs6601217; hg19: chr5-177568839;