NM_016196.4:c.2306-770C>A

Variant names:

• chr12-113921460-G-T
• rs3782455
• NM_016196.4:c.2306-770C>A

Variant summary

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

The NM_016196.4(RBM19):​c.2306-770C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,202 control chromosomes in the GnomAD database, including 352 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 (352 hom., cov: 33)
• Consequence: RBM19 NM_016196.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160
• Publications: 5 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=-0.85).
• 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 rank	MANE	Protein	UniProt
RBM19	NM_016196.4	c.2306-770C>A		intron_variant	Intron 18 of 23	ENST00000261741.10	NP_057280.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBM19	ENST00000261741.10	c.2306-770C>A		intron_variant	Intron 18 of 23	1	NM_016196.4	ENSP00000261741.5
RBM19	ENST00000392561.7	c.2306-770C>A		intron_variant	Intron 18 of 24	1		ENSP00000376344.3
RBM19	ENST00000545145.6	c.2306-770C>A		intron_variant	Intron 18 of 24	2		ENSP00000442053.2
RBM19	ENST00000552386.1	n.440-770C>A		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6507 AN: 152084 Hom.: 346 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0266

Gnomad FIN AF: 0.0191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0194

Gnomad OTH AF: 0.0523

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

GnomAD4 genome AF: 0.0429 AC: 6530 AN: 152202 Hom.: 352 Cov.: 33 AF XY: 0.0456 AC XY: 3394 AN XY: 74414

African (AFR) AF: 0.0394 AC: 1639 AN: 41548

American (AMR) AF: 0.155 AC: 2374 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3468

East Asian (EAS) AF: 0.135 AC: 700 AN: 5182

South Asian (SAS) AF: 0.0268 AC: 129 AN: 4808

European-Finnish (FIN) AF: 0.0191 AC: 202 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0194 AC: 1319 AN: 68006

Other (OTH) AF: 0.0508 AC: 107 AN: 2108

Alfa AF: 0.0304 Hom.: 326

Bravo AF: 0.0549

Asia WGS AF: 0.0910 AC: 315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.60
PhyloP100		0.016
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: rs3782455; hg19: chr12-114359265;