3-138378692-C-A

Position:

• chr3-138378692-C-A

Variant summary

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

The NM_001085049.3(MRAS):​c.193+5616C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,200 control chromosomes in the GnomAD database, including 1,396 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 0.084 (1396 hom., cov: 32)
• Consequence: MRAS NM_001085049.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.812

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRAS	NM_001085049.3	c.193+5616C>A		intron_variant		ENST00000423968.7	NP_001078518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRAS	ENST00000423968.7	c.193+5616C>A		intron_variant		1	NM_001085049.3	ENSP00000389682	P1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12822 AN: 152082 Hom.: 1395 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0844 AC: 12841 AN: 152200 Hom.: 1396 Cov.: 32 AF XY: 0.0849 AC XY: 6320 AN XY: 74428

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.0291

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.0153

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.00246

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0362 Hom.: 126

Bravo AF: 0.0926

Asia WGS AF: 0.0980 AC: 341 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	5.3
DANN	Benign	0.61

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: rs1678443; hg19: chr3-138097534;