19-48721910-C-A

Variant names:

• chr19-48721910-C-A
• rs369508351
• NM_017805.3:c.2636G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_017805.3(RASIP1):​c.2636G>T​(p.Arg879Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RASIP1 NM_017805.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225
• Publications: 0 publications found

Genes affected

RASIP1 (HGNC:24716): (Ras interacting protein 1) Enables GTPase binding activity and protein homodimerization activity. Involved in several processes, including negative regulation of Rho protein signal transduction; negative regulation of Rho-dependent protein serine/threonine kinase activity; and positive regulation of integrin activation. Located in cell-cell junction. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049870223).
• BP6: Variant 19-48721910-C-A is Benign according to our data. Variant chr19-48721910-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2245240.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASIP1	NM_017805.3	MANE Select	c.2636G>T	p.Arg879Leu	missense	Exon 11 of 12	NP_060275.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RASIP1	ENST00000222145.9	TSL:1 MANE Select	c.2636G>T	p.Arg879Leu	missense	Exon 11 of 12	ENSP00000222145.3	Q5U651
	RASIP1	ENST00000963671.1		c.2642G>T	p.Arg881Leu	missense	Exon 11 of 12	ENSP00000633730.1
	RASIP1	ENST00000862294.1		c.2636G>T	p.Arg879Leu	missense	Exon 11 of 12	ENSP00000532353.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.69
DEOGEN2	Benign	0.093	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.23
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.052
Sift	Benign	1.0	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.49		Loss of methylation at R879 (P = 0.0242)
MVP		0.14
MPC		0.74
ClinPred		0.078	T
GERP RS		-0.35
Varity_R		0.052
gMVP		0.62
Mutation Taster		=85/15	polymorphism

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: rs369508351; hg19: chr19-49225167;