chr10-16817336-C-G

Position:

• chr10-16817336-C-G

Variant summary

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

The NM_012425.4(RSU1):​c.-25G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 461,128 control chromosomes in the GnomAD database, including 14,084 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 0.28 (8654 hom., cov: 34)
  • Exomes 𝑓: 0.17 (5430 hom.)
• Consequence: RSU1 NM_012425.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSU1	NM_012425.4	c.-25G>C		5_prime_UTR_variant	1/9	ENST00000345264.10
RSU1	NM_152724.3	c.-72G>C		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSU1	ENST00000345264.10	c.-25G>C		5_prime_UTR_variant	1/9	1	NM_012425.4	P1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41878 AN: 152134 Hom.: 8637 Cov.: 34

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0416

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0906

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.167 AC: 51428 AN: 308876 Hom.: 5430 Cov.: 0 AF XY: 0.163 AC XY: 26481 AN XY: 162020

Gnomad4 AFR exome AF: 0.585

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.0251

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.0931

Gnomad4 NFE exome AF: 0.171

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.275 AC: 41941 AN: 152252 Hom.: 8654 Cov.: 34 AF XY: 0.265 AC XY: 19722 AN XY: 74460

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0906

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.255

Alfa AF: 0.0764 Hom.: 93

Bravo AF: 0.299

Asia WGS AF: 0.114 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.5
DANN	Benign	0.45

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: rs1130684; hg19: chr10-16859335; COSMIC: COSV61717576;