NM_012425.4:c.109+7564G>T

Variant names:

• chr10-16809409-C-A
• rs921742
• NM_012425.4:c.109+7564G>T

Variant summary

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

The NM_012425.4(RSU1):​c.109+7564G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,056 control chromosomes in the GnomAD database, including 1,645 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 0.13 (1645 hom., cov: 32)
• Consequence: RSU1 NM_012425.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSU1	NM_012425.4	c.109+7564G>T		intron_variant	Intron 2 of 8	ENST00000345264.10	NP_036557.1
RSU1	NM_152724.3	c.-51+7906G>T		intron_variant	Intron 1 of 7		NP_689937.2
RSU1	XM_047425617.1	c.109+7564G>T		intron_variant	Intron 1 of 6		XP_047281573.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSU1	ENST00000345264.10	c.109+7564G>T		intron_variant	Intron 2 of 8	1	NM_012425.4	ENSP00000339521.5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19066 AN: 151938 Hom.: 1639 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.108

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.125 AC: 19082 AN: 152056 Hom.: 1645 Cov.: 32 AF XY: 0.132 AC XY: 9826 AN XY: 74328

African (AFR) AF: 0.0427 AC: 1774 AN: 41502

American (AMR) AF: 0.228 AC: 3484 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1595 AN: 5162

South Asian (SAS) AF: 0.168 AC: 808 AN: 4816

European-Finnish (FIN) AF: 0.200 AC: 2103 AN: 10538

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8706 AN: 67986

Other (OTH) AF: 0.106 AC: 224 AN: 2108

Alfa AF: 0.124 Hom.: 920

Bravo AF: 0.126

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.017
DANN	Benign	0.49
PhyloP100		-2.2
Mutation Taster		=100/0	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: rs921742; hg19: chr10-16851408;