rs670523

Positions:

• chr1-155908941-A-G
• chr1-155908941-A-T

Variant summary

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

The NM_006912.6(RIT1):​c.163+1509T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,870 control chromosomes in the GnomAD database, including 21,993 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 0.48 (21993 hom., cov: 29)
• Consequence: RIT1 NM_006912.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.771

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIT1	NM_006912.6	c.163+1509T>C		intron_variant		ENST00000368323.8	NP_008843.1
RIT1	NM_001256820.2	c.55+1509T>C		intron_variant			NP_001243749.1
RIT1	NM_001256821.2	c.214+1509T>C		intron_variant			NP_001243750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIT1	ENST00000368323.8	c.163+1509T>C		intron_variant		1	NM_006912.6	ENSP00000357306	P3

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72885 AN: 151752 Hom.: 21992 Cov.: 29

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.522

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.480 AC: 72878 AN: 151870 Hom.: 21993 Cov.: 29 AF XY: 0.478 AC XY: 35504 AN XY: 74206

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.566

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.527

Alfa AF: 0.555 Hom.: 3941

Bravo AF: 0.455

Asia WGS AF: 0.335 AC: 1164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.49

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: rs670523; hg19: chr1-155878732;