rs757397798

Variant names:

• chr11-66332292-C-A
• rs757397798
• NM_004292.3:c.2336G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-66332292-C-A
• chr11-66332292-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004292.3(RIN1):​c.2336G>T​(p.Arg779Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R779Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RIN1 NM_004292.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

Genes affected

RIN1 (HGNC:18749): (Ras and Rab interactor 1) Predicted to enable small GTPase binding activity. Predicted to be involved in endocytosis; regulation of catalytic activity; and signal transduction. Predicted to act upstream of or within associative learning; memory; and negative regulation of synaptic plasticity. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03382352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIN1	NM_004292.3	c.2336G>T	p.Arg779Leu	missense_variant	Exon 10 of 10	ENST00000311320.9	NP_004283.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIN1	ENST00000311320.9	c.2336G>T	p.Arg779Leu	missense_variant	Exon 10 of 10	1	NM_004292.3	ENSP00000310406.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461698 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727166

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: 0.00000180

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
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.011
DANN	Benign	0.66
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0056	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.55	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.71	N;N
REVEL	Benign	0.0060
Sift	Benign	0.27	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0	B;B
Vest4		0.080
MutPred		0.23		Loss of solvent accessibility (P = 0.0606);.;
MVP		0.040
MPC		0.32
ClinPred		0.049	T
GERP RS		-8.9
Varity_R		0.028
gMVP		0.082

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: rs757397798; hg19: chr11-66099763;