chr3-12626285-A-T

Variant names:

• chr3-12626285-A-T
• rs11711419
• NM_002880.4:c.-26-7538T>A

Variant summary

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

The NM_002880.4(RAF1):​c.-26-7538T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 150,118 control chromosomes in the GnomAD database, including 3,671 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 0.21 (3671 hom., cov: 28)
• Consequence: RAF1 NM_002880.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAF1	NM_002880.4	c.-26-7538T>A		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.-26-7538T>A		intron_variant	Intron 1 of 16	1	NM_002880.4	ENSP00000251849.4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 31743 AN: 150004 Hom.: 3668 Cov.: 28

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.212 AC: 31753 AN: 150118 Hom.: 3671 Cov.: 28 AF XY: 0.208 AC XY: 15203 AN XY: 73218

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0262

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.205

Alfa AF: 0.192 Hom.: 329

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11711419; hg19: chr3-12667784;