rs6597256

Variant names:

• chr6-7207774-G-A
• rs6597256
• NM_001003699.4:c.426-3030G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003699.4(RREB1):​c.426-3030G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 152,078 control chromosomes in the GnomAD database, including 24,519 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 0.56 (24519 hom., cov: 33)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 5 publications found

Genes affected

RREB1 (HGNC:10449): (ras responsive element binding protein 1) The protein encoded by this gene is a zinc finger transcription factor that binds to RAS-responsive elements (RREs) of gene promoters. It has been shown that the calcitonin gene promoter contains an RRE and that the encoded protein binds there and increases expression of calcitonin, which may be involved in Ras/Raf-mediated cell differentiation. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

RREB1 Gene-Disease associations (from GenCC):

• RASopathy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RREB1	NM_001003699.4	MANE Select	c.426-3030G>A		intron	N/A	NP_001003699.1	Q92766-2
	RREB1	NM_001003698.4		c.426-3030G>A		intron	N/A	NP_001003698.1	Q92766-1
	RREB1	NM_001168344.2		c.426-3030G>A		intron	N/A	NP_001161816.1	Q92766-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RREB1	ENST00000379938.7	TSL:1 MANE Select	c.426-3030G>A		intron	N/A	ENSP00000369270.2	Q92766-2
	RREB1	ENST00000349384.10	TSL:1	c.426-3030G>A		intron	N/A	ENSP00000305560.10	Q92766-1
	RREB1	ENST00000379933.7	TSL:1	c.426-3030G>A		intron	N/A	ENSP00000369265.3	Q92766-1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84634 AN: 151960 Hom.: 24467 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.557 AC: 84745 AN: 152078 Hom.: 24519 Cov.: 33 AF XY: 0.565 AC XY: 41976 AN XY: 74350

African (AFR) AF: 0.684 AC: 28383 AN: 41482

American (AMR) AF: 0.506 AC: 7730 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1594 AN: 3470

East Asian (EAS) AF: 0.797 AC: 4116 AN: 5166

South Asian (SAS) AF: 0.689 AC: 3326 AN: 4826

European-Finnish (FIN) AF: 0.573 AC: 6049 AN: 10548

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31839 AN: 67982

Other (OTH) AF: 0.504 AC: 1065 AN: 2112

Alfa AF: 0.522 Hom.: 3712

Bravo AF: 0.555

Asia WGS AF: 0.747 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6597256; hg19: chr6-7208007;