3-50091966-C-T

Variant summary

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

The NM_005778.4(RBM5):c.18-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 1,428,510 control chromosomes in the GnomAD database, including 213,142 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 0.56 (24619 hom., cov: 31)
  • Exomes 𝑓: 0.53 (188523 hom.)
• Consequence: RBM5 NM_005778.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86

Genes affected

RBM5 (HGNC:9902): (RNA binding motif protein 5) This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer. [provided by RefSeq, Oct 2011]

RBM6 (HGNC:9903): (RNA binding motif protein 6) Enables RNA binding activity. Predicted to be involved in mRNA splicing, via spliceosome. Predicted to be active in nucleus. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM5	NM_005778.4	c.18-77C>T		intron_variant		ENST00000347869.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM5	ENST00000347869.8	c.18-77C>T		intron_variant		1	NM_005778.4	P1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85373 AN: 151884 Hom.: 24590 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.550

GnomAD3 exomes AF: 0.609 AC: 148950 AN: 244710 Hom.: 47195 AF XY: 0.607 AC XY: 80582 AN XY: 132718

Gnomad AFR exome AF: 0.578

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.662

Gnomad EAS exome AF: 0.853

Gnomad SAS exome AF: 0.771

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.500

Gnomad OTH exome AF: 0.569

GnomAD4 exome AF: 0.533 AC: 680163 AN: 1276506 Hom.: 188523 Cov.: 18 AF XY: 0.539 AC XY: 347332 AN XY: 644466

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.764

Gnomad4 FIN exome AF: 0.550

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.551

GnomAD4 genome AF: 0.562 AC: 85454 AN: 152004 Hom.: 24619 Cov.: 31 AF XY: 0.574 AC XY: 42605 AN XY: 74268

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.771

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.547

Alfa AF: 0.520 Hom.: 21973

Bravo AF: 0.561

Asia WGS AF: 0.737 AC: 2565 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	0.0040
Dann	Benign	0.41

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: rs2013208; hg19: chr3-50129399;