11-73711834-A-G

Position:

• chr11-73711834-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198896.2(RAB6A):​c.402-4321T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,160 control chromosomes in the GnomAD database, including 48,406 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 0.80 (48406 hom., cov: 32)
• Consequence: RAB6A NM_198896.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.816

Genes affected

RAB6A (HGNC:9786): (RAB6A, member RAS oncogene family) This gene encodes a member of the RAB family, which belongs to the small GTPase superfamily. GTPases of the RAB family bind to various effectors to regulate the targeting and fusion of transport carriers to acceptor compartments. This protein is located at the Golgi apparatus, which regulates trafficking in both a retrograde (from early endosomes and Golgi to the endoplasmic reticulum) and an anterograde (from the Golgi to the plasma membrane) directions. Myosin II is an effector of this protein in these processes. This protein is also involved in assembly of human cytomegalovirus (HCMV) by interacting with the cellular protein Bicaudal D1, which interacts with the HCMV virion tegument protein, pp150. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

RAB6A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAB6A	NM_198896.2	c.402-4321T>C		intron_variant		ENST00000336083.8	NP_942599.1
RAB6A	NM_002869.5	c.402-4321T>C		intron_variant			NP_002860.2
RAB6A	NM_001243719.2	c.303-4321T>C		intron_variant			NP_001230648.1
RAB6A	NM_001243718.2	c.183+9012T>C		intron_variant			NP_001230647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAB6A	ENST00000336083.8	c.402-4321T>C		intron_variant		1	NM_198896.2	ENSP00000336850.3

Frequencies

GnomAD3 genomes AF: 0.796 AC: 120982 AN: 152042 Hom.: 48378 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.796 AC: 121065 AN: 152160 Hom.: 48406 Cov.: 32 AF XY: 0.796 AC XY: 59225 AN XY: 74400

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.868

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.775

Alfa AF: 0.809 Hom.: 19206

Bravo AF: 0.791

Asia WGS AF: 0.772 AC: 2680 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.92

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: rs2140892; hg19: chr11-73422879;