4-52862521-A-C

Variant names:

• chr4-52862521-A-C
• rs1309285076
• NM_023940.3:c.14A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023940.3(RASL11B):​c.14A>C​(p.Gln5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASL11B NM_023940.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

Genes affected

RASL11B (HGNC:23804): (RAS like family 11 member B) Predicted to enable G protein activity; GTP binding activity; and transforming growth factor beta receptor binding activity. Predicted to act upstream of or within negative regulation of transforming growth factor beta receptor signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

LINC01618 (HGNC:27195): (long intergenic non-protein coding RNA 1618)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19336957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASL11B	NM_023940.3	c.14A>C	p.Gln5Pro	missense_variant	Exon 1 of 4	ENST00000248706.5	NP_076429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASL11B	ENST00000248706.5	c.14A>C	p.Gln5Pro	missense_variant	Exon 1 of 4	1	NM_023940.3	ENSP00000248706.3
RASL11B	ENST00000515677.1	n.190A>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
LINC01618	ENST00000650700.1	n.989-747A>C		intron_variant	Intron 8 of 10
LINC01618	ENST00000652441.1	n.504-747A>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14A>C (p.Q5P) alteration is located in exon 1 (coding exon 1) of the RASL11B gene. This alteration results from a A to C substitution at nucleotide position 14, causing the glutamine (Q) at amino acid position 5 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.032
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.098	T
Polyphen		0.0010	B
Vest4		0.44
MutPred		0.37		Loss of sheet (P = 0.0126);
MVP		0.66
MPC		0.48
ClinPred		0.73	D
GERP RS		3.5
Varity_R		0.44
gMVP		0.87

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: rs1309285076; hg19: chr4-53728688;