chr9-136830775-C-T

Variant names:

• chr9-136830775-C-T
• rs2811749
• NM_024718.5:c.459-946C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

MIR4292 (HGNC:38348): (microRNA 4292) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

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 (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RABL6	NM_024718.5	c.459-946C>T		intron_variant	Intron 5 of 14	ENST00000311502.12	NP_078994.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RABL6	ENST00000311502.12	c.459-946C>T		intron_variant	Intron 5 of 14	1	NM_024718.5	ENSP00000311134.7
RABL6	ENST00000357466.6	c.459-946C>T		intron_variant	Intron 5 of 9	1		ENSP00000350056.2

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

African (AFR) AF: 0.700 AC: 29069 AN: 41536

American (AMR) AF: 0.759 AC: 11607 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2778 AN: 3472

East Asian (EAS) AF: 0.818 AC: 4232 AN: 5174

South Asian (SAS) AF: 0.765 AC: 3691 AN: 4826

European-Finnish (FIN) AF: 0.805 AC: 8543 AN: 10610

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.792 AC: 53846 AN: 68010

Other (OTH) AF: 0.764 AC: 1614 AN: 2112

Alfa AF: 0.776 Hom.: 58145

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
PhyloP100		-1.2
RBP_binding_hub_radar		0.85
RBP_regulation_power_radar		3.1
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: rs2811749; hg19: chr9-139725227; COSMIC: COSV61039858; COSMIC: COSV61039858;