chr3-50091966-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005778.4(RBM5):​c.18-77C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,279,344 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 7.8e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.82e-7 AC: 1 AN: 1279344 Hom.: 0 Cov.: 18 AF XY: 0.00000155 AC XY: 1 AN XY: 645802

African (AFR) AF: 0.00 AC: 0 AN: 29582

American (AMR) AF: 0.00 AC: 0 AN: 44198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25020

East Asian (EAS) AF: 0.00 AC: 0 AN: 38834

South Asian (SAS) AF: 0.00 AC: 0 AN: 82102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5450

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 948186

Other (OTH) AF: 0.00 AC: 0 AN: 54276

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0040
DANN	Benign	0.36
PhyloP100		-1.9

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;