rs3765595

chr10-16764546-A-C

Variant summary

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

The NM_012425.4(RSU1):c.161-36T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,594,874 control chromosomes in the GnomAD database, including 25,700 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 0.20 (3460 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22240 hom.)
• Consequence: RSU1 NM_012425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

Genes affected

RSU1 (HGNC:10464): (Ras suppressor protein 1) This gene encodes a protein that is involved in the Ras signal transduction pathway, growth inhibition, and nerve-growth factor induced differentiation processes, as determined in mouse and human cell line studies. In mouse, the encoded protein was initially isolated based on its ability to inhibit v-Ras transformation. Multiple alternatively spliced transcript variants for this gene have been reported; one of these variants was found only in glioma tumors. [provided by RefSeq, Jul 2008]

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 (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSU1	NM_012425.4	c.161-36T>G		intron_variant		ENST00000345264.10
RSU1	NM_152724.3	c.2-36T>G		intron_variant
RSU1	XM_047425617.1	c.161-36T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSU1	ENST00000345264.10	c.161-36T>G		intron_variant		1	NM_012425.4	P1

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30540 AN: 152076 Hom.: 3456 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.222

GnomAD3 exomes AF: 0.155 AC: 37305 AN: 241292 Hom.: 3500 AF XY: 0.153 AC XY: 19955 AN XY: 130448

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.198

Gnomad EAS exome AF: 0.0180

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.128

Gnomad NFE exome AF: 0.182

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.169 AC: 243653 AN: 1442680 Hom.: 22240 Cov.: 30 AF XY: 0.166 AC XY: 119152 AN XY: 716138

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.0225

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.178

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.201 AC: 30564 AN: 152194 Hom.: 3460 Cov.: 32 AF XY: 0.196 AC XY: 14580 AN XY: 74430

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0183

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.223

Alfa AF: 0.184 Hom.: 593

Bravo AF: 0.211

Asia WGS AF: 0.0760 AC: 262 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	0.25
Dann	Benign	0.39

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: rs3765595; hg19: chr10-16806545;