chr10-16695157-TGG-T

Variant names:

• chr10-16695157-TGG-T
• rs56715139
• NM_012425.4:c.599-4_599-3delCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_012425.4(RSU1):​c.599-4_599-3delCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,190,774 control chromosomes in the GnomAD database, including 739 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.042 (346 hom., cov: 17)
  • Exomes 𝑓: 0.014 (393 hom.)
• Consequence: RSU1 NM_012425.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.33
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012425.4. 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
	RSU1	NM_012425.4	MANE Select	c.599-4_599-3delCC		splice_region intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.440-4_440-3delCC		splice_region intron	N/A	NP_689937.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSU1	ENST00000345264.10	TSL:1 MANE Select	c.599-4_599-3delCC		splice_region intron	N/A	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.599-4_599-3delCC		splice_region intron	N/A	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.440-4_440-3delCC		splice_region intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 5433 AN: 128160 Hom.: 346 Cov.: 17

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00287

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.00590

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0106

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.0347

GnomAD4 exome AF: 0.0137 AC: 14545 AN: 1062550 Hom.: 393 AF XY: 0.0137 AC XY: 7217 AN XY: 527592

African (AFR) AF: 0.133 AC: 3391 AN: 25454

American (AMR) AF: 0.0160 AC: 437 AN: 27242

Ashkenazi Jewish (ASJ) AF: 0.00998 AC: 176 AN: 17642

East Asian (EAS) AF: 0.148 AC: 4105 AN: 27824

South Asian (SAS) AF: 0.0153 AC: 916 AN: 59814

European-Finnish (FIN) AF: 0.0189 AC: 667 AN: 35384

Middle Eastern (MID) AF: 0.0212 AC: 91 AN: 4296

European-Non Finnish (NFE) AF: 0.00449 AC: 3686 AN: 821642

Other (OTH) AF: 0.0249 AC: 1076 AN: 43252

GnomAD4 genome AF: 0.0424 AC: 5443 AN: 128224 Hom.: 346 Cov.: 17 AF XY: 0.0416 AC XY: 2543 AN XY: 61130

African (AFR) AF: 0.130 AC: 4495 AN: 34602

American (AMR) AF: 0.0147 AC: 192 AN: 13050

Ashkenazi Jewish (ASJ) AF: 0.00287 AC: 9 AN: 3140

East Asian (EAS) AF: 0.108 AC: 458 AN: 4254

South Asian (SAS) AF: 0.00595 AC: 21 AN: 3532

European-Finnish (FIN) AF: 0.0151 AC: 103 AN: 6824

Middle Eastern (MID) AF: 0.0114 AC: 3 AN: 264

European-Non Finnish (NFE) AF: 0.00165 AC: 99 AN: 60068

Other (OTH) AF: 0.0360 AC: 63 AN: 1750

Alfa AF: 0.0137 Hom.: 109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3
Mutation Taster		=92/8	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: rs56715139; hg19: chr10-16737156; COSMIC: COSV61710718;