rs41433646

chr12-113867459-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RBM19	NM_016196.4	c.2559-8563C>T		intron_variant		ENST00000261741.10
LOC124903025	XR_007063468.1	n.4938G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBM19	ENST00000261741.10	c.2559-8563C>T		intron_variant		1	NM_016196.4	P1
RBM19	ENST00000392561.7	c.2559-8563C>T		intron_variant		1		P1
	ENST00000671241.1	n.416-2353G>A		intron_variant, non_coding_transcript_variant
RBM19	ENST00000545145.6	c.2559-8563C>T		intron_variant		2		P1

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

Gnomad4 AFR AF: 0.0606

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0123 Hom.: 5

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

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