rs2287692

Positions:

• chr19-40783851-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016154.5(RAB4B):​c.275+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,569,146 control chromosomes in the GnomAD database, including 16,435 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 0.11 (1151 hom., cov: 30)
  • Exomes 𝑓: 0.14 (15284 hom.)
• Consequence: RAB4B NM_016154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601

Genes affected

RAB4B (HGNC:9782): (RAB4B, member RAS oncogene family) Predicted to enable G protein activity and GTP binding activity. Involved in glucose import. Located in insulin-responsive compartment; perinuclear region of cytoplasm; and recycling endosome. [provided by Alliance of Genome Resources, Apr 2022]

RAB4B-EGLN2 (HGNC:44465): (RAB4B-EGLN2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring RAB4B (RAB4B, member RAS oncogene family) and EGLN2 (egl nine homolog 2) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

MIA-RAB4B (HGNC:48352): (MIA-RAB4B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MIA (melanoma inhibitory activity) and RAB4B (RAB4B, member RAS oncogene family) genes on chromosome 19. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ENSG00000282951 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB4B	NM_016154.5	c.275+11G>A		intron_variant		ENST00000357052.8	NP_057238.3
MIA-RAB4B	NR_037775.1	n.637+11G>A		intron_variant
RAB4B-EGLN2	NR_037791.1	n.432+11G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB4B	ENST00000357052.8	c.275+11G>A		intron_variant		1	NM_016154.5	ENSP00000349560.2
RAB4B-EGLN2	ENST00000594136.2	n.275+11G>A		intron_variant		2		ENSP00000469872.1
MIA-RAB4B	ENST00000600729.2	n.*235+11G>A		intron_variant		5		ENSP00000472384.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16495 AN: 151618 Hom.: 1148 Cov.: 30

Gnomad AFR AF: 0.0334

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0748

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.135 AC: 29932 AN: 221640 Hom.: 2269 AF XY: 0.140 AC XY: 16652 AN XY: 119332

Gnomad AFR exome AF: 0.0307

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0703

Gnomad SAS exome AF: 0.187

Gnomad FIN exome AF: 0.140

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.130

GnomAD4 exome AF: 0.144 AC: 203498 AN: 1417412 Hom.: 15284 Cov.: 46 AF XY: 0.145 AC XY: 101309 AN XY: 699468

Gnomad4 AFR exome AF: 0.0293

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.182

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.146

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.109 AC: 16507 AN: 151734 Hom.: 1151 Cov.: 30 AF XY: 0.110 AC XY: 8133 AN XY: 74130

Gnomad4 AFR AF: 0.0334

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0743

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.107

Alfa AF: 0.136 Hom.: 1943

Bravo AF: 0.102

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.75

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: rs2287692; hg19: chr19-41289756; COSMIC: COSV63825188; COSMIC: COSV63825188;