rs2070446

Variant names:

• chr22-23693783-C-G
• rs2070446
• NM_153615.2:c.721C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-23693783-C-G
• chr22-23693783-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153615.2(RGL4):​c.721C>G​(p.His241Asp) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RGL4 NM_153615.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• Publications: 37 publications found

Genes affected

RGL4 (HGNC:31911): (ral guanine nucleotide dissociation stimulator like 4) This oncogene encodes a protein similar to guanine nucleotide exchange factor Ral guanine dissociation stimulator. Increased expression of this gene leads to translocation of the encoded protein to the cell membrane. The encoded protein can activate several pathways, including the Ras-Raf-MEK-ERK cascade. [provided by RefSeq, Jul 2016]

GUSBP11 (HGNC:):

GUSBP11 (HGNC:42325): (GUSB pseudogene 11) This transcribed pseudogene is similar to two functional genes. The 5' portion of the pseudogene is related to glucuronidase, beta, and the 3' portion is related to immunoglobulin lambda-like polypeptide 1. [provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2365449).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153615.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL4	NM_153615.2	MANE Select	c.721C>G	p.His241Asp	missense	Exon 4 of 11	NP_705843.1	Q8IZJ4-1
	RGL4	NM_001329424.3		c.721C>G	p.His241Asp	missense	Exon 4 of 12	NP_001316353.1
	GUSBP11	NR_024448.2		n.2561+336G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGL4	ENST00000290691.10	TSL:1 MANE Select	c.721C>G	p.His241Asp	missense	Exon 4 of 11	ENSP00000290691.5	Q8IZJ4-1
	RGL4	ENST00000423392.5	TSL:1	c.721C>G	p.His241Asp	missense	Exon 4 of 12	ENSP00000402142.1	E7EPT8
	RGL4	ENST00000441897.5	TSL:2	n.721C>G		non_coding_transcript_exon	Exon 6 of 14	ENSP00000396252.1	E9PH21

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 161911

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N
PhyloP100		1.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Benign	0.16
Sift	Uncertain	0.010	D
Sift4G	Benign	0.11	T
Polyphen		0.56	P
Vest4		0.30
MutPred		0.41		Gain of relative solvent accessibility (P = 0.0507)
MVP		0.35
MPC		0.22
ClinPred		0.44	T
GERP RS		-1.1
Varity_R		0.19
gMVP		0.50
Mutation Taster		=100/0	polymorphism

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: rs2070446; hg19: chr22-24035970;