rs2604894

Positions:

• chr19-40786499-A-G

Variant summary

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

The NM_016154.5(RAB4B):​c.431-166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 989,550 control chromosomes in the GnomAD database, including 153,208 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 0.55 (23218 hom., cov: 29)
  • Exomes 𝑓: 0.55 (129990 hom.)
• Consequence: RAB4B NM_016154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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]

RAB4B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB4B	NM_016154.5	c.431-166A>G		intron_variant		ENST00000357052.8	NP_057238.3
MIA-RAB4B	NR_037775.1	n.793-166A>G		intron_variant
RAB4B-EGLN2	NR_037791.1	n.588-166A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB4B	ENST00000357052.8	c.431-166A>G		intron_variant		1	NM_016154.5	ENSP00000349560.2
RAB4B-EGLN2	ENST00000594136.2	n.431-166A>G		intron_variant		2		ENSP00000469872.1
MIA-RAB4B	ENST00000600729.2	n.*391-166A>G		intron_variant		5		ENSP00000472384.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83145 AN: 151548 Hom.: 23189 Cov.: 29

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.553 AC: 463743 AN: 837882 Hom.: 129990 Cov.: 11 AF XY: 0.547 AC XY: 230197 AN XY: 420726

Gnomad4 AFR exome AF: 0.476

Gnomad4 AMR exome AF: 0.683

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.669

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.615

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.549 AC: 83225 AN: 151668 Hom.: 23218 Cov.: 29 AF XY: 0.551 AC XY: 40837 AN XY: 74084

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.546

Alfa AF: 0.533 Hom.: 2816

Bravo AF: 0.555

Asia WGS AF: 0.587 AC: 2039 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	1.3
DANN	Benign	0.63

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: rs2604894; hg19: chr19-41292404;