19-40796801-C-T

Variant names:

• chr19-40796801-C-T
• rs7937
• NM_016154.5:c.*247C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_016154.5(RAB4B):​c.*247C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,600 control chromosomes in the GnomAD database, including 19,732 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 0.49 (19617 hom., cov: 32)
  • Exomes 𝑓: 0.63 (115 hom.)
• Consequence: RAB4B NM_016154.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 72 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]

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-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]

ENSG00000282951 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4B	NM_016154.5	MANE Select	c.*247C>T		3_prime_UTR	Exon 8 of 8	NP_057238.3
	MIA-RAB4B	NR_037775.1		n.1251C>T		non_coding_transcript_exon	Exon 10 of 10
	RAB4B-EGLN2	NR_037791.1		n.815-3538C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB4B	ENST00000357052.8	TSL:1 MANE Select	c.*247C>T		3_prime_UTR	Exon 8 of 8	ENSP00000349560.2	P61018-1
	RAB4B	ENST00000378307.9	TSL:1	n.*368C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000367557.4	F6SQB9
	MIA-RAB4B	ENST00000600729.2	TSL:5	n.*849C>T		non_coding_transcript_exon	Exon 11 of 11	ENSP00000472384.1	W4VSR3

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74438 AN: 151876 Hom.: 19611 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.629 AC: 381 AN: 606 Hom.: 115 Cov.: 0 AF XY: 0.605 AC XY: 231 AN XY: 382

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.333 AC: 2 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.665 AC: 290 AN: 436

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.544 AC: 74 AN: 136

Other (OTH) AF: 0.556 AC: 10 AN: 18

GnomAD4 genome AF: 0.490 AC: 74477 AN: 151994 Hom.: 19617 Cov.: 32 AF XY: 0.494 AC XY: 36733 AN XY: 74294

African (AFR) AF: 0.294 AC: 12198 AN: 41462

American (AMR) AF: 0.562 AC: 8588 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2094 AN: 3472

East Asian (EAS) AF: 0.637 AC: 3287 AN: 5158

South Asian (SAS) AF: 0.418 AC: 2016 AN: 4818

European-Finnish (FIN) AF: 0.637 AC: 6730 AN: 10572

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37749 AN: 67924

Other (OTH) AF: 0.503 AC: 1060 AN: 2106

Alfa AF: 0.536 Hom.: 97631

Bravo AF: 0.483

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.097
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	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: rs7937; hg19: chr19-41302706; COSMIC: COSV58279921; COSMIC: COSV58279921;