chr10-16755034-A-G

Variant names:

• chr10-16755034-A-G
• rs7910261
• NM_012425.4:c.282-45T>C

Variant summary

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

The NM_012425.4(RSU1):​c.282-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,169,496 control chromosomes in the GnomAD database, including 58,928 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 0.42 (17639 hom., cov: 32)
  • Exomes 𝑓: 0.27 (41289 hom.)
• Consequence: RSU1 NM_012425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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.282-45T>C		intron	N/A	NP_036557.1	Q15404-1
	RSU1	NM_152724.3		c.123-45T>C		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.282-45T>C		intron	N/A	ENSP00000339521.5	Q15404-1
	RSU1	ENST00000377921.7	TSL:1	c.282-45T>C		intron	N/A	ENSP00000367154.3	Q15404-1
	RSU1	ENST00000602389.1	TSL:1	c.123-45T>C		intron	N/A	ENSP00000473588.1	Q15404-2

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63443 AN: 152018 Hom.: 17571 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.405

GnomAD2 exomes AF: 0.298 AC: 69838 AN: 234722 AF XY: 0.287

Gnomad AFR exome AF: 0.807

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.415

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.293

GnomAD4 exome AF: 0.267 AC: 271354 AN: 1017360 Hom.: 41289 Cov.: 13 AF XY: 0.264 AC XY: 138644 AN XY: 524410

African (AFR) AF: 0.816 AC: 19361 AN: 23720

American (AMR) AF: 0.243 AC: 9807 AN: 40436

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 5591 AN: 22330

East Asian (EAS) AF: 0.379 AC: 14086 AN: 37134

South Asian (SAS) AF: 0.254 AC: 18824 AN: 74232

European-Finnish (FIN) AF: 0.224 AC: 11804 AN: 52668

Middle Eastern (MID) AF: 0.336 AC: 1118 AN: 3326

European-Non Finnish (NFE) AF: 0.247 AC: 177382 AN: 718304

Other (OTH) AF: 0.296 AC: 13381 AN: 45210

GnomAD4 genome AF: 0.418 AC: 63579 AN: 152136 Hom.: 17639 Cov.: 32 AF XY: 0.412 AC XY: 30661 AN XY: 74384

African (AFR) AF: 0.800 AC: 33202 AN: 41502

American (AMR) AF: 0.349 AC: 5332 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 914 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2049 AN: 5156

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4824

European-Finnish (FIN) AF: 0.227 AC: 2399 AN: 10586

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17218 AN: 68006

Other (OTH) AF: 0.410 AC: 867 AN: 2114

Alfa AF: 0.320 Hom.: 2255

Bravo AF: 0.445

Asia WGS AF: 0.387 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.048
DANN	Benign	0.29
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

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: rs7910261; hg19: chr10-16797033; COSMIC: COSV61716466;