chr19-48730078-G-A

Variant names:

• chr19-48730078-G-A
• rs281407
• NM_017805.3:c.1180-488C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017805.3(RASIP1):​c.1180-488C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 151,742 control chromosomes in the GnomAD database, including 7,780 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 0.31 (7780 hom., cov: 29)
• Consequence: RASIP1 NM_017805.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 21 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]

LOC124904737 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RASIP1	NM_017805.3	c.1180-488C>T		intron_variant	Intron 4 of 11	ENST00000222145.9	NP_060275.2
LOC124904737	XR_007067286.1	n.226-1188G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RASIP1	ENST00000222145.9	c.1180-488C>T		intron_variant	Intron 4 of 11	1	NM_017805.3	ENSP00000222145.3
RASIP1	ENST00000599291.1	c.414+5118C>T		intron_variant	Intron 2 of 2	3		ENSP00000471633.1
RASIP1	ENST00000594232.1	n.577-488C>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47395 AN: 151624 Hom.: 7787 Cov.: 29

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.312 AC: 47401 AN: 151742 Hom.: 7780 Cov.: 29 AF XY: 0.314 AC XY: 23289 AN XY: 74138

African (AFR) AF: 0.236 AC: 9743 AN: 41362

American (AMR) AF: 0.331 AC: 5045 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3464

East Asian (EAS) AF: 0.633 AC: 3255 AN: 5146

South Asian (SAS) AF: 0.323 AC: 1553 AN: 4802

European-Finnish (FIN) AF: 0.323 AC: 3395 AN: 10502

Middle Eastern (MID) AF: 0.250 AC: 72 AN: 288

European-Non Finnish (NFE) AF: 0.326 AC: 22173 AN: 67920

Other (OTH) AF: 0.295 AC: 620 AN: 2100

Alfa AF: 0.319 Hom.: 4686

Bravo AF: 0.308

Asia WGS AF: 0.442 AC: 1533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.86
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs281407; hg19: chr19-49233335;