rs1720819

Positions:

• chr3-138381697-T-G

Variant summary

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

The NM_001085049.3(MRAS):​c.193+8621T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,170 control chromosomes in the GnomAD database, including 3,249 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 0.18 (3249 hom., cov: 32)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.257

Genes affected

MRAS (HGNC:7227): (muscle RAS oncogene homolog) This gene encodes a member of the Ras family of small GTPases. These membrane-associated proteins function as signal transducers in multiple processes including cell growth and differentiation, and dysregulation of Ras signaling has been associated with many types of cancer. The encoded protein may play a role in the tumor necrosis factor-alpha and MAP kinase signaling pathways. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRAS	NM_001085049.3	c.193+8621T>G		intron_variant		ENST00000423968.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRAS	ENST00000423968.7	c.193+8621T>G		intron_variant		1	NM_001085049.3	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27364 AN: 152052 Hom.: 3242 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0914

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.180 AC: 27398 AN: 152170 Hom.: 3249 Cov.: 32 AF XY: 0.176 AC XY: 13112 AN XY: 74404

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.0952

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.0905

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.158

Alfa AF: 0.124 Hom.: 789

Bravo AF: 0.184

Asia WGS AF: 0.155 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.9
DANN	Benign	0.66

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: rs1720819; hg19: chr3-138100539;