12-113913750-T-C

Variant names:

• chr12-113913750-T-C
• rs4767161
• NM_016196.4:c.2558+1219A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016196.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM19	NM_016196.4	MANE Select	c.2558+1219A>G		intron	N/A	NP_057280.2
	RBM19	NM_001146698.2		c.2558+1219A>G		intron	N/A	NP_001140170.1
	RBM19	NM_001146699.2		c.2558+1219A>G		intron	N/A	NP_001140171.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM19	ENST00000261741.10	TSL:1 MANE Select	c.2558+1219A>G		intron	N/A	ENSP00000261741.5
	RBM19	ENST00000392561.7	TSL:1	c.2558+1219A>G		intron	N/A	ENSP00000376344.3
	RBM19	ENST00000545145.6	TSL:2	c.2558+1219A>G		intron	N/A	ENSP00000442053.2

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

African (AFR) AF: 0.857 AC: 35593 AN: 41548

American (AMR) AF: 0.905 AC: 13855 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3221 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5100 AN: 5174

South Asian (SAS) AF: 0.945 AC: 4559 AN: 4826

European-Finnish (FIN) AF: 0.816 AC: 8643 AN: 10594

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.854 AC: 58081 AN: 68022

Other (OTH) AF: 0.879 AC: 1858 AN: 2114

Alfa AF: 0.864 Hom.: 93807

Bravo AF: 0.874

Asia WGS AF: 0.939 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.49
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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: rs4767161; hg19: chr12-114351555;