rs2604894

Variant names:

• chr19-40786499-A-G
• rs2604894
• NM_016154.5:c.431-166A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-40786499-A-G
• chr19-40786499-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016154.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4B	NM_016154.5	MANE Select	c.431-166A>G		intron	N/A	NP_057238.3
	MIA-RAB4B	NR_037775.1		n.793-166A>G		intron	N/A
	RAB4B-EGLN2	NR_037791.1		n.588-166A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4B	ENST00000357052.8	TSL:1 MANE Select	c.431-166A>G		intron	N/A	ENSP00000349560.2
	RAB4B	ENST00000378307.9	TSL:1	n.276-166A>G		intron	N/A	ENSP00000367557.4
	RAB4B-EGLN2	ENST00000594136.2	TSL:2	n.431-166A>G		intron	N/A	ENSP00000469872.1

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

African (AFR) AF: 0.476 AC: 9493 AN: 19952

American (AMR) AF: 0.683 AC: 16948 AN: 24798

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 9254 AN: 16168

East Asian (EAS) AF: 0.669 AC: 20067 AN: 30006

South Asian (SAS) AF: 0.424 AC: 24367 AN: 57432

European-Finnish (FIN) AF: 0.615 AC: 19219 AN: 31258

Middle Eastern (MID) AF: 0.522 AC: 1469 AN: 2814

European-Non Finnish (NFE) AF: 0.554 AC: 341926 AN: 617636

Other (OTH) AF: 0.555 AC: 21000 AN: 37818

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

African (AFR) AF: 0.486 AC: 20085 AN: 41306

American (AMR) AF: 0.629 AC: 9591 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2021 AN: 3472

East Asian (EAS) AF: 0.686 AC: 3512 AN: 5120

South Asian (SAS) AF: 0.430 AC: 2066 AN: 4800

European-Finnish (FIN) AF: 0.617 AC: 6520 AN: 10560

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37537 AN: 67858

Other (OTH) AF: 0.546 AC: 1150 AN: 2106

Alfa AF: 0.537 Hom.: 8636

Bravo AF: 0.555

Asia WGS AF: 0.587 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		-0.29
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: rs2604894; hg19: chr19-41292404;