6-7231610-GAC-AAT

Variant names:

• chr6-7231610-GAC-AAT
• NM_001003699.4:c.3511_3513delGACinsAAT
• RREB1 p.Asp1171Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001003699.4(RREB1):​c.3511_3513delGACinsAAT​(p.Asp1171Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RREB1 NM_001003699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.33
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.3511_3513delGACinsAAT	p.Asp1171Asn	missense	N/A	NP_001003699.1	Q92766-2
	RREB1	NM_001003698.4		c.3511_3513delGACinsAAT	p.Asp1171Asn	missense	N/A	NP_001003698.1	Q92766-1
	RREB1	NM_001168344.2		c.3511_3513delGACinsAAT	p.Asp1171Asn	missense	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.3511_3513delGACinsAAT	p.Asp1171Asn	missense	N/A	ENSP00000369270.2	Q92766-2
	RREB1	ENST00000349384.10	TSL:1	c.3511_3513delGACinsAAT	p.Asp1171Asn	missense	N/A	ENSP00000305560.10	Q92766-1
	RREB1	ENST00000379933.7	TSL:1	c.3511_3513delGACinsAAT	p.Asp1171Asn	missense	N/A	ENSP00000369265.3	Q92766-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-7231843;