chr3-50115923-T-C

Variant names:

• chr3-50115923-T-C
• rs1138536
• NM_005778.4:c.2037T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005778.4(RBM5):​c.2037T>C​(p.Tyr679Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,612,388 control chromosomes in the GnomAD database, including 307,161 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 0.65 (33139 hom., cov: 32)
  • Exomes 𝑓: 0.61 (274022 hom.)
• Consequence: RBM5 NM_005778.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 43 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]

SEMA3F-AS1 (HGNC:40518): (SEMA3F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005778.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM5	NM_005778.4	MANE Select	c.2037T>C	p.Tyr679Tyr	synonymous	Exon 22 of 25	NP_005769.1
	RBM5	NR_036627.3		n.2127T>C		non_coding_transcript_exon	Exon 21 of 24
	SEMA3F-AS1	NR_135301.1		n.*99A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM5	ENST00000347869.8	TSL:1 MANE Select	c.2037T>C	p.Tyr679Tyr	synonymous	Exon 22 of 25	ENSP00000343054.3
	RBM5	ENST00000852698.1		c.2037T>C	p.Tyr679Tyr	synonymous	Exon 22 of 26	ENSP00000522757.1
	RBM5	ENST00000852694.1		c.2043T>C	p.Tyr681Tyr	synonymous	Exon 22 of 25	ENSP00000522753.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99339 AN: 151984 Hom.: 33093 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.829

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.675 AC: 169668 AN: 251410 AF XY: 0.673

Gnomad AFR exome AF: 0.726

Gnomad AMR exome AF: 0.761

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.884

Gnomad FIN exome AF: 0.621

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.636

GnomAD4 exome AF: 0.606 AC: 884777 AN: 1460286 Hom.: 274022 Cov.: 45 AF XY: 0.611 AC XY: 443722 AN XY: 726532

African (AFR) AF: 0.733 AC: 24529 AN: 33442

American (AMR) AF: 0.752 AC: 33616 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.733 AC: 19156 AN: 26134

East Asian (EAS) AF: 0.871 AC: 34552 AN: 39684

South Asian (SAS) AF: 0.822 AC: 70914 AN: 86224

European-Finnish (FIN) AF: 0.617 AC: 32960 AN: 53404

Middle Eastern (MID) AF: 0.651 AC: 3755 AN: 5768

European-Non Finnish (NFE) AF: 0.565 AC: 627656 AN: 1110574

Other (OTH) AF: 0.624 AC: 37639 AN: 60342

GnomAD4 genome AF: 0.654 AC: 99438 AN: 152102 Hom.: 33139 Cov.: 32 AF XY: 0.662 AC XY: 49198 AN XY: 74328

African (AFR) AF: 0.729 AC: 30244 AN: 41494

American (AMR) AF: 0.679 AC: 10374 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2572 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4582 AN: 5172

South Asian (SAS) AF: 0.829 AC: 3994 AN: 4816

European-Finnish (FIN) AF: 0.618 AC: 6530 AN: 10558

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39103 AN: 67996

Other (OTH) AF: 0.637 AC: 1343 AN: 2108

Alfa AF: 0.607 Hom.: 62836

Bravo AF: 0.655

Asia WGS AF: 0.799 AC: 2778 AN: 3478

EpiCase AF: 0.581

EpiControl AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs1138536; hg19: chr3-50153356;