NM_016196.4:c.2762G>A

Variant names:

• chr12-113844691-C-T
• rs2075387
• NM_016196.4:c.2762G>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.2762G>A​(p.Arg921Gln) variant causes a missense change. The variant allele was found at a frequency of 0.261 in 1,609,256 control chromosomes in the GnomAD database, including 56,295 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 0.24 (4788 hom., cov: 33)
  • Exomes 𝑓: 0.26 (51507 hom.)
• Consequence: RBM19 NM_016196.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72
• Publications: 24 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 (MetaRNN=0.0017284453).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM19	NM_016196.4	MANE Select	c.2762G>A	p.Arg921Gln	missense	Exon 23 of 24	NP_057280.2
	RBM19	NM_001146698.2		c.2762G>A	p.Arg921Gln	missense	Exon 23 of 25	NP_001140170.1
	RBM19	NM_001146699.2		c.2762G>A	p.Arg921Gln	missense	Exon 23 of 25	NP_001140171.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBM19	ENST00000261741.10	TSL:1 MANE Select	c.2762G>A	p.Arg921Gln	missense	Exon 23 of 24	ENSP00000261741.5
	RBM19	ENST00000392561.7	TSL:1	c.2762G>A	p.Arg921Gln	missense	Exon 23 of 25	ENSP00000376344.3
	RBM19	ENST00000970408.1		c.2762G>A	p.Arg921Gln	missense	Exon 23 of 27	ENSP00000640467.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37231 AN: 152096 Hom.: 4782 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.245 AC: 59587 AN: 242782 AF XY: 0.252

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.129

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.266

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.263 AC: 383432 AN: 1457042 Hom.: 51507 Cov.: 34 AF XY: 0.265 AC XY: 192028 AN XY: 724590

African (AFR) AF: 0.183 AC: 6100 AN: 33398

American (AMR) AF: 0.182 AC: 8082 AN: 44318

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 7480 AN: 26054

East Asian (EAS) AF: 0.158 AC: 6263 AN: 39572

South Asian (SAS) AF: 0.293 AC: 25112 AN: 85644

European-Finnish (FIN) AF: 0.329 AC: 17121 AN: 52100

Middle Eastern (MID) AF: 0.332 AC: 1906 AN: 5738

European-Non Finnish (NFE) AF: 0.267 AC: 295941 AN: 1110026

Other (OTH) AF: 0.256 AC: 15427 AN: 60192

GnomAD4 genome AF: 0.245 AC: 37256 AN: 152214 Hom.: 4788 Cov.: 33 AF XY: 0.248 AC XY: 18436 AN XY: 74414

African (AFR) AF: 0.181 AC: 7506 AN: 41562

American (AMR) AF: 0.207 AC: 3165 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.143 AC: 737 AN: 5164

South Asian (SAS) AF: 0.299 AC: 1444 AN: 4828

European-Finnish (FIN) AF: 0.343 AC: 3638 AN: 10594

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18829 AN: 67986

Other (OTH) AF: 0.259 AC: 548 AN: 2114

Alfa AF: 0.259 Hom.: 17443

Bravo AF: 0.230

TwinsUK AF: 0.264 AC: 978

ALSPAC AF: 0.257 AC: 991

ESP6500AA AF: 0.176 AC: 776

ESP6500EA AF: 0.270 AC: 2321

ExAC AF: 0.248 AC: 30086

Asia WGS AF: 0.208 AC: 728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.7
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.15
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.26
MPC		0.20
ClinPred		0.020	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.41
gMVP		0.55
Mutation Taster		=93/7	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: rs2075387; hg19: chr12-114282496; COSMIC: COSV55687682;