3-133839310-A-C

Variant names:

• chr3-133839310-A-C
• rs2280673
• NM_016577.4:c.401+196T>G

Variant summary

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

The NM_016577.4(RAB6B):​c.401+196T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 152,180 control chromosomes in the GnomAD database, including 27,839 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 0.60 (27839 hom., cov: 34)
• Consequence: RAB6B NM_016577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.489
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.647 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.401+196T>G		intron	N/A	NP_057661.3
	RAB6B	NM_001363953.1		c.362+196T>G		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.401+196T>G		intron	N/A	ENSP00000285208.4
	RAB6B	ENST00000543906.5	TSL:1	c.401+196T>G		intron	N/A	ENSP00000437797.1
	RAB6B	ENST00000486858.5	TSL:2	c.362+196T>G		intron	N/A	ENSP00000419381.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91198 AN: 152062 Hom.: 27837 Cov.: 34

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.591

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

GnomAD4 genome AF: 0.600 AC: 91235 AN: 152180 Hom.: 27839 Cov.: 34 AF XY: 0.592 AC XY: 44054 AN XY: 74410

African (AFR) AF: 0.568 AC: 23592 AN: 41510

American (AMR) AF: 0.490 AC: 7497 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2224 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2093 AN: 5172

South Asian (SAS) AF: 0.463 AC: 2235 AN: 4826

European-Finnish (FIN) AF: 0.676 AC: 7158 AN: 10596

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

European-Non Finnish (NFE) AF: 0.652 AC: 44304 AN: 67986

Other (OTH) AF: 0.584 AC: 1235 AN: 2114

Alfa AF: 0.621 Hom.: 59857

Bravo AF: 0.586

Asia WGS AF: 0.448 AC: 1559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.67
PhyloP100		-0.49
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: rs2280673; hg19: chr3-133558154;