chr19-40796801-C-T

Position:

• chr19-40796801-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB4B	NM_016154.5	c.*247C>T		3_prime_UTR_variant	8/8	ENST00000357052.8	NP_057238.3
MIA-RAB4B	NR_037775.1	n.1251C>T		non_coding_transcript_exon_variant	10/10
RAB4B-EGLN2	NR_037791.1	n.815-3538C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB4B	ENST00000357052.8	c.*247C>T		3_prime_UTR_variant	8/8	1	NM_016154.5	ENSP00000349560.2
MIA-RAB4B	ENST00000600729.2	n.*849C>T		non_coding_transcript_exon_variant	11/11	5		ENSP00000472384.1
MIA-RAB4B	ENST00000600729.2	n.*849C>T		3_prime_UTR_variant	11/11	5		ENSP00000472384.1
RAB4B-EGLN2	ENST00000594136.2	n.*16-3538C>T		intron_variant		2		ENSP00000469872.1

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

Gnomad4 AMR exome AF: 0.333

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.665

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.556

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.603

Gnomad4 EAS AF: 0.637

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.503

Alfa AF: 0.545 Hom.: 49978

Bravo AF: 0.483

Asia WGS AF: 0.542 AC: 1885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	14
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7937; hg19: chr19-41302706; COSMIC: COSV58279921; COSMIC: COSV58279921;