rs2023953

chr3-50066484-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_005777.3(RBM6):c.2925G>A(p.Gln975=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,370 control chromosomes in the GnomAD database, including 8,518 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 0.094 (744 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7774 hom.)
• Consequence: RBM6 NM_005777.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

Genes affected

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP7: Synonymous conserved (PhyloP=1.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM6	NM_005777.3	c.2925G>A	p.Gln975=	synonymous_variant	17/21	ENST00000266022.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM6	ENST00000266022.9	c.2925G>A	p.Gln975=	synonymous_variant	17/21	1	NM_005777.3	P1

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14266 AN: 152166 Hom.: 741 Cov.: 32

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0569

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0946

GnomAD3 exomes AF: 0.0974 AC: 24022 AN: 246580 Hom.: 1272 AF XY: 0.0941 AC XY: 12584 AN XY: 133790

Gnomad AFR exome AF: 0.0751

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.0505

Gnomad SAS exome AF: 0.0508

Gnomad FIN exome AF: 0.101

Gnomad NFE exome AF: 0.105

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.101 AC: 148052 AN: 1461086 Hom.: 7774 Cov.: 32 AF XY: 0.0994 AC XY: 72235 AN XY: 726812

Gnomad4 AFR exome AF: 0.0744

Gnomad4 AMR exome AF: 0.127

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.0589

Gnomad4 SAS exome AF: 0.0530

Gnomad4 FIN exome AF: 0.0989

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0971

GnomAD4 genome AF: 0.0938 AC: 14284 AN: 152284 Hom.: 744 Cov.: 32 AF XY: 0.0930 AC XY: 6921 AN XY: 74454

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0572

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0936

Alfa AF: 0.104 Hom.: 1320

Bravo AF: 0.0950

Asia WGS AF: 0.0640 AC: 223 AN: 3478

EpiCase AF: 0.109

EpiControl AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	5.6
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2023953; hg19: chr3-50103917; COSMIC: COSV56487889; COSMIC: COSV56487889;