X-47562002-G-T

Variant summary

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

The NM_001654.5(ARAF):c.-60+751G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.25 (2994 hom., 4655 hem., cov: 16)
• Consequence: ARAF NM_001654.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

Genes affected

ARAF (HGNC:646): (A-Raf proto-oncogene, serine/threonine kinase) Enables protein serine/threonine kinase activity. Involved in negative regulation of apoptotic process; regulation of TOR signaling; and regulation of cellular protein metabolic process. Predicted to be active in cytosol and mitochondrion. Biomarker of high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARAF	NM_001654.5	c.-60+751G>T		intron_variant		ENST00000377045.9
ARAF	NM_001256196.2	c.-60+751G>T		intron_variant
ARAF	NM_001256197.2	c.-60+751G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARAF	ENST00000377045.9	c.-60+751G>T		intron_variant		1	NM_001654.5	P1
ARAF	ENST00000377039.2	c.-60+751G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 23705 AN: 95221 Hom.: 2990 Cov.: 16 AF XY: 0.217 AC XY: 4637 AN XY: 21361

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.249 AC: 23726 AN: 95252 Hom.: 2994 Cov.: 16 AF XY: 0.217 AC XY: 4655 AN XY: 21404

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.258

Alfa AF: 0.188 Hom.: 14416

Bravo AF: 0.281

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.5
Dann	Benign	0.70

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: rs2283736; hg19: chrX-47421401;