rs371820097

Variant names:

• chr3-12583765-CTGTTTGTT-C
• rs371820097
• NM_002880.4:c.*741_*748delAACAAACA

Your query was ambiguous. Multiple possible variants found:

• chr3-12583765-CTGTTTGTT-C
• chr3-12583765-CTGTTTGTT-CTGTT
• chr3-12583765-CTGTTTGTT-CTGTTTGTTTGTT
• chr3-12583765-CTGTTTGTT-CTGTTTGTTTGTTTGTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002880.4(RAF1):​c.*741_*748delAACAAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 233,466 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0030 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: RAF1 NM_002880.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 453 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAF1	NM_002880.4	c.*741_*748delAACAAACA		3_prime_UTR_variant	Exon 17 of 17	ENST00000251849.9	NP_002871.1
MKRN2	NM_014160.5	c.*1513_*1520delTGTTTGTT		downstream_gene_variant		ENST00000170447.12	NP_054879.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAF1	ENST00000251849	c.*741_*748delAACAAACA		3_prime_UTR_variant	Exon 17 of 17	1	NM_002880.4	ENSP00000251849.4
MKRN2	ENST00000170447.12	c.*1513_*1520delTGTTTGTT		downstream_gene_variant		1	NM_014160.5	ENSP00000170447.7

Frequencies

GnomAD3 genomes AF: 0.00296 AC: 450 AN: 152032 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00979

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.000652 AC: 53 AN: 81312 Hom.: 0 AF XY: 0.000507 AC XY: 19 AN XY: 37440

Gnomad4 AFR exome AF: 0.00592

Gnomad4 AMR exome AF: 0.000801

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000881

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000299

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00298 AC: 453 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.00314 AC XY: 234 AN XY: 74418

Gnomad4 AFR AF: 0.00984

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.0000623 Hom.: 5

Bravo AF: 0.00341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371820097; hg19: chr3-12625264;