rs6795441

Variant names:

• chr3-12661063-A-G
• rs6795441
• NM_002880.4:c.-27+2750T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-12661063-A-G
• chr3-12661063-A-T

Variant summary

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

The NM_002880.4(RAF1):​c.-27+2750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,036 control chromosomes in the GnomAD database, including 17,264 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 0.47 (17264 hom., cov: 33)
• Consequence: RAF1 NM_002880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

Genes affected

RAF1 (HGNC:9829): (Raf-1 proto-oncogene, serine/threonine kinase) This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAF1	NM_002880.4	c.-27+2750T>C		intron_variant	Intron 1 of 16	ENST00000251849.9	NP_002871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAF1	ENST00000251849.9	c.-27+2750T>C		intron_variant	Intron 1 of 16	1	NM_002880.4	ENSP00000251849.4

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70872 AN: 151918 Hom.: 17240 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.467 AC: 70941 AN: 152036 Hom.: 17264 Cov.: 33 AF XY: 0.475 AC XY: 35275 AN XY: 74316

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.460

Alfa AF: 0.450 Hom.: 13977

Bravo AF: 0.463

Asia WGS AF: 0.770 AC: 2673 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.91

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: rs6795441; hg19: chr3-12702562;