11-73719556-A-G

Variant names:

• chr11-73719556-A-G
• rs11235876
• NM_198896.2:c.184-838T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_198896.2(RAB6A):​c.184-838T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,040 control chromosomes in the GnomAD database, including 19,022 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 0.48 (19022 hom., cov: 32)
• Consequence: RAB6A NM_198896.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB6A	NM_198896.2	c.184-838T>C		intron_variant	Intron 3 of 7	ENST00000336083.8	NP_942599.1
RAB6A	NM_002869.5	c.184-666T>C		intron_variant	Intron 3 of 7		NP_002860.2
RAB6A	NM_001243719.2	c.85-666T>C		intron_variant	Intron 3 of 7		NP_001230648.1
RAB6A	NM_001243718.2	c.183+1290T>C		intron_variant	Intron 3 of 4		NP_001230647.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB6A	ENST00000336083.8	c.184-838T>C		intron_variant	Intron 3 of 7	1	NM_198896.2	ENSP00000336850.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73223 AN: 151922 Hom.: 19010 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.491

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

GnomAD4 genome AF: 0.482 AC: 73265 AN: 152040 Hom.: 19022 Cov.: 32 AF XY: 0.482 AC XY: 35842 AN XY: 74312

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.556

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.493

Alfa AF: 0.515 Hom.: 4094

Bravo AF: 0.477

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.5
DANN	Benign	0.68

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: rs11235876; hg19: chr11-73430601;