3-133870480-C-T

Variant names:

• chr3-133870480-C-T
• rs9835973
• NM_016577.4:c.71-5838G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016577.4(RAB6B):​c.71-5838G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,100 control chromosomes in the GnomAD database, including 1,814 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 0.13 (1814 hom., cov: 32)
• Consequence: RAB6B NM_016577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 12 publications found

Genes affected

RAB6B (HGNC:14902): (RAB6B, member RAS oncogene family) Enables myosin V binding activity. Predicted to be involved in Golgi vesicle transport; intracellular protein transport; and retrograde transport, endosome to Golgi. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016577.4. 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
	RAB6B	NM_016577.4	MANE Select	c.71-5838G>A		intron	N/A	NP_057661.3
	RAB6B	NM_001363953.1		c.32-5838G>A		intron	N/A	NP_001350882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAB6B	ENST00000285208.9	TSL:1 MANE Select	c.71-5838G>A		intron	N/A	ENSP00000285208.4
	RAB6B	ENST00000543906.5	TSL:1	c.71-5838G>A		intron	N/A	ENSP00000437797.1
	RAB6B	ENST00000486858.5	TSL:2	c.32-5838G>A		intron	N/A	ENSP00000419381.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20507 AN: 151982 Hom.: 1809 Cov.: 32

Gnomad AFR AF: 0.0385

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.167

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20524 AN: 152100 Hom.: 1814 Cov.: 32 AF XY: 0.140 AC XY: 10440 AN XY: 74336

African (AFR) AF: 0.0385 AC: 1598 AN: 41522

American (AMR) AF: 0.237 AC: 3623 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.138 AC: 713 AN: 5170

South Asian (SAS) AF: 0.194 AC: 931 AN: 4810

European-Finnish (FIN) AF: 0.200 AC: 2111 AN: 10572

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10557 AN: 67966

Other (OTH) AF: 0.168 AC: 353 AN: 2106

Alfa AF: 0.155 Hom.: 7128

Bravo AF: 0.138

Asia WGS AF: 0.156 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.2
DANN	Benign	0.64
PhyloP100		0.34
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: rs9835973; hg19: chr3-133589324;