12-113913750-T-C

Variant summary

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

The NM_016196.4(RBM19):c.2558+1219A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,260 control chromosomes in the GnomAD database, including 57,348 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 0.87 (57348 hom., cov: 33)
• Consequence: RBM19 NM_016196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBM19	NM_016196.4	c.2558+1219A>G		intron_variant		ENST00000261741.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM19	ENST00000261741.10	c.2558+1219A>G		intron_variant		1	NM_016196.4	P1
RBM19	ENST00000392561.7	c.2558+1219A>G		intron_variant		1		P1
RBM19	ENST00000545145.6	c.2558+1219A>G		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131927 AN: 152142 Hom.: 57295 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.943

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.867 AC: 132036 AN: 152260 Hom.: 57348 Cov.: 33 AF XY: 0.869 AC XY: 64671 AN XY: 74446

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.928

Gnomad4 EAS AF: 0.986

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.854

Gnomad4 OTH AF: 0.879

Alfa AF: 0.863 Hom.: 73718

Bravo AF: 0.874

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.41
Dann	Benign	0.49

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: rs4767161; hg19: chr12-114351555;