rs2282301

Positions:

• chr1-155898834-G-A
• chr1-155898834-G-T

Variant summary

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

The NM_006912.6(RIT1):​c.*1554C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 191,540 control chromosomes in the GnomAD database, including 10,420 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 0.30 (7361 hom., cov: 30)
  • Exomes 𝑓: 0.34 (3059 hom.)
• Consequence: RIT1 NM_006912.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT1	NM_006912.6	c.*1554C>T		3_prime_UTR_variant	6/6	ENST00000368323.8	NP_008843.1
RIT1	NM_001256820.2	c.*1554C>T		3_prime_UTR_variant	5/5		NP_001243749.1
RIT1	NM_001256821.2	c.*1554C>T		3_prime_UTR_variant	6/6		NP_001243750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT1	ENST00000368323.8	c.*1554C>T		3_prime_UTR_variant	6/6	1	NM_006912.6	ENSP00000357306	P3
RIT1	ENST00000461050.6	c.*1943C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	5		ENSP00000476319
RIT1	ENST00000704061.1	c.*1885C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5			ENSP00000515664
RIT1	ENST00000651853.1			downstream_gene_variant				ENSP00000498685	A1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44716 AN: 151550 Hom.: 7348 Cov.: 30

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.339 AC: 13506 AN: 39872 Hom.: 3059 Cov.: 0 AF XY: 0.336 AC XY: 6194 AN XY: 18428

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.388

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.749

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.206

Gnomad4 NFE exome AF: 0.244

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.295 AC: 44755 AN: 151668 Hom.: 7361 Cov.: 30 AF XY: 0.299 AC XY: 22120 AN XY: 74090

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.291

Alfa AF: 0.275 Hom.: 8620

Bravo AF: 0.308

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2282301; hg19: chr1-155868625;