chr19-48720863-C-T

Variant names:

• chr19-48720863-C-T
• rs34800326
• NM_017805.3:c.2827G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_017805.3(RASIP1):​c.2827G>A​(p.Asp943Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,614,048 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (2 hom.)
• Consequence: RASIP1 NM_017805.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.76
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030408323).
• BP6: Variant 19-48720863-C-T is Benign according to our data. Variant chr19-48720863-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3044744.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 175 AD gene.

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.2827G>A	p.Asp943Asn	missense	Exon 12 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.2827G>A	p.Asp943Asn	missense	Exon 12 of 12	ENSP00000222145.3	Q5U651
	RASIP1	ENST00000963671.1		c.2863G>A	p.Asp955Asn	missense	Exon 12 of 12	ENSP00000633730.1
	RASIP1	ENST00000862294.1		c.2857G>A	p.Asp953Asn	missense	Exon 12 of 12	ENSP00000532353.1

Frequencies

GnomAD3 genomes AF: 0.00115 AC: 175 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00218

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000872 AC: 219 AN: 251144 AF XY: 0.000884

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.00171

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00182 AC: 2662 AN: 1461728 Hom.: 2 Cov.: 31 AF XY: 0.00175 AC XY: 1270 AN XY: 727158

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.000425 AC: 19 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.0000563 AC: 3 AN: 53278

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00232 AC: 2575 AN: 1111992

Other (OTH) AF: 0.000878 AC: 53 AN: 60396

GnomAD4 genome AF: 0.00115 AC: 175 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.000900 AC XY: 67 AN XY: 74476

African (AFR) AF: 0.000481 AC: 20 AN: 41588

American (AMR) AF: 0.000196 AC: 3 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00218 AC: 148 AN: 68016

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00162 Hom.: 4

Bravo AF: 0.00110

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00302 AC: 26

ExAC AF: 0.000758 AC: 92

EpiCase AF: 0.00196

EpiControl AF: 0.00190

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RASIP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.098	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		2.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.11
Sift	Benign	0.13	T
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.29
MVP		0.27
MPC		1.5
ClinPred		0.044	T
GERP RS		5.5
Varity_R		0.18
gMVP		0.59
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs34800326; hg19: chr19-49224120;