rs41433646

Variant names:

• chr12-113867459-G-A
• rs41433646
• NM_016196.4:c.2559-8563C>T

Variant summary

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

The NM_016196.4(RBM19):​c.2559-8563C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 152,272 control chromosomes in the GnomAD database, including 91 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 0.018 (91 hom., cov: 33)
• Consequence: RBM19 NM_016196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82
• Publications: 1 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]

LOC124903025 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBM19	NM_016196.4	c.2559-8563C>T		intron_variant	Intron 21 of 23	ENST00000261741.10	NP_057280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM19	ENST00000261741.10	c.2559-8563C>T		intron_variant	Intron 21 of 23	1	NM_016196.4	ENSP00000261741.5
RBM19	ENST00000392561.7	c.2559-8563C>T		intron_variant	Intron 21 of 24	1		ENSP00000376344.3
RBM19	ENST00000545145.6	c.2559-8563C>T		intron_variant	Intron 21 of 24	2		ENSP00000442053.2
ENSG00000287229	ENST00000671241.1	n.416-2353G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2689 AN: 152154 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0177 AC: 2690 AN: 152272 Hom.: 91 Cov.: 33 AF XY: 0.0172 AC XY: 1281 AN XY: 74454

African (AFR) AF: 0.0606 AC: 2517 AN: 41544

American (AMR) AF: 0.00693 AC: 106 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68032

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0141 Hom.: 6

Bravo AF: 0.0201

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.68
PhyloP100		-3.8
Mutation Taster		=100/0	polymorphism

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: rs41433646; hg19: chr12-114305264; COSMIC: COSV55688857;