19-48721227-C-T

Position:

• chr19-48721227-C-T

Variant summary

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

The NM_017805.3(RASIP1):​c.2693-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,844 control chromosomes in the GnomAD database, including 12,065 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 0.39 (12065 hom., cov: 30)
• Consequence: RASIP1 NM_017805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASIP1	NM_017805.3	c.2693-230G>A		intron_variant		ENST00000222145.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASIP1	ENST00000222145.9	c.2693-230G>A		intron_variant		1	NM_017805.3	P1
RASIP1	ENST00000601530.1	n.1187-230G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58625 AN: 151726 Hom.: 12068 Cov.: 30

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.386 AC: 58657 AN: 151844 Hom.: 12065 Cov.: 30 AF XY: 0.392 AC XY: 29047 AN XY: 74186

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.390

Alfa AF: 0.363 Hom.: 12563

Bravo AF: 0.394

Asia WGS AF: 0.636 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.035
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs281393; hg19: chr19-49224484;