Variant rs3729931 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000251849.9(RAF1):c.1669-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,613,362 control chromosomes in the GnomAD database, including 110,021 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14949 hom., cov: 31)

Exomes 𝑓: 0.35 ( 95072 hom. )

Consequence

RAF1
ENST00000251849.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.69

Variant links:

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]

RAF1 links:

MKRN2 (HGNC:7113): (makorin ring finger protein 2) This gene encodes a probable E3 ubiquitin ligase containing several zinc finger domains, that is a member of the makorin RING zinc-finger protein family. This gene overlaps the v-raf-1 murine leukemia viral oncogene homolog 1 (RAF1) gene in an antisense orientation and may have a co-regulatory function with RAF1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

MKRN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 3-12585017-G-A is Benign according to our data. Variant chr3-12585017-G-A is described in ClinVar as [Benign]. Clinvar id is 40624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAF1	NM_002880.4 linkuse as main transcript	c.1669-36C>T		intron_variant		ENST00000251849.9	NP_002871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAF1	ENST00000251849.9 linkuse as main transcript	c.1669-36C>T		intron_variant		1	NM_002880.4	ENSP00000251849	P3	P04049-1

Frequencies

GnomAD3 genomes

AF:

0.424

AC:

64437

AN:

151906

Hom.:

14925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.608

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.363

Gnomad OTH

AF:

0.406

GnomAD3 exomes

AF:

0.353

AC:

88513

AN:

250924

Hom.:

17686

AF XY:

0.338

AC XY:

45801

AN XY:

135612

show subpopulations

Gnomad AFR exome

AF:

0.615

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.0555

Gnomad SAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.382

Gnomad NFE exome

AF:

0.358

Gnomad OTH exome

AF:

0.361

GnomAD4 exome

AF:

0.351

AC:

513149

AN:

1461336

Hom.:

95072

Cov.:

AF XY:

0.344

AC XY:

250334

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.624

Gnomad4 AMR exome

AF:

0.477

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.0626

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.386

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.351

GnomAD4 genome

AF:

0.424

AC:

64513

AN:

152026

Hom.:

14949

Cov.:

AF XY:

0.419

AC XY:

31128

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.440

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.0525

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.363

Gnomad4 OTH

AF:

0.410

Alfa

AF:

0.359

Hom.:

19606

Bravo

AF:

0.440

Asia WGS

AF:

0.220

AC:

767

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Mar 18, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.6

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over