1-155898834-G-A

Variant names:

• chr1-155898834-G-A
• rs2282301
• NM_006912.6:c.*1554C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 34 publications found

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]

RIT1 Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome 8

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006912.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIT1	NM_006912.6	MANE Select	c.*1554C>T		3_prime_UTR	Exon 6 of 6	NP_008843.1
	RIT1	NM_001256821.2		c.*1554C>T		3_prime_UTR	Exon 6 of 6	NP_001243750.1
	RIT1	NM_001256820.2		c.*1554C>T		3_prime_UTR	Exon 5 of 5	NP_001243749.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIT1	ENST00000368323.8	TSL:1 MANE Select	c.*1554C>T		3_prime_UTR	Exon 6 of 6	ENSP00000357306.3
	RIT1	ENST00000461050.6	TSL:5	n.*1943C>T		non_coding_transcript_exon	Exon 7 of 7	ENSP00000476319.1
	RIT1	ENST00000704061.1		n.*1885C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000515664.1

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

African (AFR) AF: 0.321 AC: 517 AN: 1610

American (AMR) AF: 0.388 AC: 397 AN: 1022

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 576 AN: 2576

East Asian (EAS) AF: 0.749 AC: 5143 AN: 6868

South Asian (SAS) AF: 0.305 AC: 108 AN: 354

European-Finnish (FIN) AF: 0.206 AC: 7 AN: 34

Middle Eastern (MID) AF: 0.159 AC: 39 AN: 246

European-Non Finnish (NFE) AF: 0.244 AC: 5815 AN: 23846

Other (OTH) AF: 0.273 AC: 904 AN: 3316

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

African (AFR) AF: 0.317 AC: 13123 AN: 41380

American (AMR) AF: 0.326 AC: 4953 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 786 AN: 3462

East Asian (EAS) AF: 0.752 AC: 3885 AN: 5166

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4818

European-Finnish (FIN) AF: 0.249 AC: 2611 AN: 10466

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17069 AN: 67882

Other (OTH) AF: 0.291 AC: 612 AN: 2106

Alfa AF: 0.275 Hom.: 20825

Bravo AF: 0.308

Asia WGS AF: 0.514 AC: 1788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.53
PhyloP100		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs2282301; hg19: chr1-155868625;