rs3825209

Positions:

• chr12-113913252-T-C
• chr12-113913252-T-G

Variant summary

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

The ENST00000261741.10(RBM19):​c.2558+1717A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0428 in 152,144 control chromosomes in the GnomAD database, including 347 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 0.043 (347 hom., cov: 32)
• Consequence: RBM19 ENST00000261741.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

RBM19 (HGNC:29098): (RNA binding motif protein 19) This gene encodes a nucleolar protein that contains six RNA-binding motifs. The encoded protein may be involved in regulating ribosome biogenesis. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM19	NM_016196.4	c.2558+1717A>G		intron_variant		ENST00000261741.10	NP_057280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM19	ENST00000261741.10	c.2558+1717A>G		intron_variant		1	NM_016196.4	ENSP00000261741	P1
RBM19	ENST00000392561.7	c.2558+1717A>G		intron_variant		1		ENSP00000376344	P1
RBM19	ENST00000545145.6	c.2558+1717A>G		intron_variant		2		ENSP00000442053	P1

Frequencies

GnomAD3 genomes AF: 0.0427 AC: 6485 AN: 152026 Hom.: 341 Cov.: 32

Gnomad AFR AF: 0.0393

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0260

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0531

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0428 AC: 6508 AN: 152144 Hom.: 347 Cov.: 32 AF XY: 0.0454 AC XY: 3379 AN XY: 74392

Gnomad4 AFR AF: 0.0393

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0262

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0194

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.00932 Hom.: 0

Bravo AF: 0.0548

Asia WGS AF: 0.0910 AC: 314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.4
DANN	Benign	0.72

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: rs3825209; hg19: chr12-114351057;