ENST00000609492.1:c.-117G>C

Variant names:

• chr1-155910878-C-G
• ENST00000609492.1:c.-117G>C

Variant summary

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

The ENST00000609492.1(RIT1):​c.-117G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,334 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: RIT1 ENST00000609492.1 5_prime_UTR
• Scores: Splicing: ADA: 0.00006147
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

Genes affected

RIT1 (HGNC:10023): (Ras like without CAAX 1) This gene encodes a member of a subfamily of Ras-related GTPases. The encoded protein is involved in regulating p38 MAPK-dependent signaling cascades related to cellular stress. This protein also cooperates with nerve growth factor to promote neuronal development and regeneration. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

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=0.16798595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIT1	NM_006912.6	c.-43-74G>C		intron_variant	Intron 1 of 5	ENST00000368323.8	NP_008843.1
RIT1	NM_001256821.2	c.8G>C	p.Arg3Thr	missense_variant, splice_region_variant	Exon 1 of 6		NP_001243750.1
RIT1	NM_001256820.2	c.-3+365G>C		intron_variant	Intron 1 of 4		NP_001243749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIT1	ENST00000368323.8	c.-43-74G>C		intron_variant	Intron 1 of 5	1	NM_006912.6	ENSP00000357306.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433334 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 711006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.5
DANN	Benign	0.89
Eigen	Benign	0.055
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.0060
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.24
MutPred		0.38		Loss of sheet (P = 0.0315);
MVP		0.24
MPC		1.1
ClinPred		0.091	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000061
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-155880669;