rs281408

Positions:

• chr19-48730149-C-A
• chr19-48730149-C-G
• chr19-48730149-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.1180-559G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,444 control chromosomes in the GnomAD database, including 14,326 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 0.42 (14326 hom., cov: 28)
• Consequence: RASIP1 NM_017805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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]

LOC124904737 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RASIP1	NM_017805.3	c.1180-559G>T		intron_variant		ENST00000222145.9
LOC124904737	XR_007067286.1	n.226-1117C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RASIP1	ENST00000222145.9	c.1180-559G>T		intron_variant		1	NM_017805.3	P1
RASIP1	ENST00000599291.1	c.415+5047G>T		intron_variant		3
RASIP1	ENST00000594232.1	n.577-559G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63815 AN: 151326 Hom.: 14333 Cov.: 28

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.421 AC: 63830 AN: 151444 Hom.: 14326 Cov.: 28 AF XY: 0.425 AC XY: 31458 AN XY: 73966

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.427

Alfa AF: 0.440 Hom.: 9402

Bravo AF: 0.423

Asia WGS AF: 0.658 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.8
DANN	Benign	0.75

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: rs281408; hg19: chr19-49233406;