3-50091966-C-T

Variant names:

• chr3-50091966-C-T
• rs2013208
• NM_005778.4:c.18-77C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 86 publications found

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

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 = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM5	NM_005778.4	c.18-77C>T		intron_variant	Intron 2 of 24	ENST00000347869.8	NP_005769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM5	ENST00000347869.8	c.18-77C>T		intron_variant	Intron 2 of 24	1	NM_005778.4	ENSP00000343054.3

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

GnomAD2 exomes AF: 0.609 AC: 148950 AN: 244710 AF XY: 0.607

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 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

African (AFR) AF: 0.584 AC: 17223 AN: 29516

American (AMR) AF: 0.712 AC: 31462 AN: 44176

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 16410 AN: 25000

East Asian (EAS) AF: 0.846 AC: 32863 AN: 38824

South Asian (SAS) AF: 0.764 AC: 62722 AN: 82052

European-Finnish (FIN) AF: 0.550 AC: 28383 AN: 51636

Middle Eastern (MID) AF: 0.596 AC: 3242 AN: 5444

European-Non Finnish (NFE) AF: 0.484 AC: 458003 AN: 945686

Other (OTH) AF: 0.551 AC: 29855 AN: 54172

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

African (AFR) AF: 0.582 AC: 24092 AN: 41428

American (AMR) AF: 0.625 AC: 9541 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2295 AN: 3466

East Asian (EAS) AF: 0.858 AC: 4447 AN: 5184

South Asian (SAS) AF: 0.771 AC: 3716 AN: 4820

European-Finnish (FIN) AF: 0.552 AC: 5815 AN: 10532

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33813 AN: 68000

Other (OTH) AF: 0.547 AC: 1151 AN: 2106

Alfa AF: 0.528 Hom.: 61639

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
PhyloP100		-1.9
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: rs2013208; hg19: chr3-50129399;