rs2811749

chr9-136830775-C-T

Variant summary

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

The NM_024718.5(RABL6):c.459-946C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,246 control chromosomes in the GnomAD database, including 44,511 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 0.76 (44511 hom., cov: 35)
• Consequence: RABL6 NM_024718.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

RABL6 (HGNC:24703): (RAB, member RAS oncogene family like 6) This gene encodes a member of the Ras superfamily of small GTPases. The encoded protein binds to both GTP and GDP and may play a role in cell growth and survival. Overexpression of this gene may play a role in breast cancer tumorigenesis, and pseudogenes of this gene are located on the long arm of chromosome 2 and the short arm of chromosome 18. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RABL6	NM_024718.5	c.459-946C>T		intron_variant		ENST00000311502.12
RABL6	NM_001173988.2	c.459-946C>T		intron_variant
RABL6	NM_001173989.4	c.459-946C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RABL6	ENST00000311502.12	c.459-946C>T		intron_variant		1	NM_024718.5	P3

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116262 AN: 152126 Hom.: 44501 Cov.: 35

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.759

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.764 AC: 116316 AN: 152246 Hom.: 44511 Cov.: 35 AF XY: 0.765 AC XY: 56920 AN XY: 74446

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.764

Alfa AF: 0.780 Hom.: 45076

Bravo AF: 0.757

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.48
Dann	Benign	0.56
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.1

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: rs2811749; hg19: chr9-139725227; COSMIC: COSV61039858; COSMIC: COSV61039858;