6-7118757-A-G

Variant names:

• chr6-7118757-A-G
• rs11755724
• NM_001003699.4:c.-285+10697A>G

Variant summary

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

The NM_001003699.4(RREB1):​c.-285+10697A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 146,774 control chromosomes in the GnomAD database, including 19,948 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 0.48 (19948 hom., cov: 26)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 41 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):

• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RREB1	NM_001003699.4	c.-285+10697A>G		intron_variant	Intron 1 of 12	ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4	c.-285+10697A>G		intron_variant	Intron 1 of 11		NP_001003698.1
RREB1	NM_001168344.2	c.-285+10989A>G		intron_variant	Intron 1 of 11		NP_001161816.1
RREB1	NM_001003700.2	c.-285+10697A>G		intron_variant	Intron 1 of 11		NP_001003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7	c.-285+10697A>G		intron_variant	Intron 1 of 12	1	NM_001003699.4	ENSP00000369270.2

Frequencies

GnomAD3 genomes AF: 0.483 AC: 70929 AN: 146702 Hom.: 19956 Cov.: 26

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.00738

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.604

Gnomad MID AF: 0.632

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.483 AC: 70931 AN: 146774 Hom.: 19948 Cov.: 26 AF XY: 0.478 AC XY: 34072 AN XY: 71274

African (AFR) AF: 0.235 AC: 9231 AN: 39288

American (AMR) AF: 0.521 AC: 7636 AN: 14646

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1901 AN: 3442

East Asian (EAS) AF: 0.00760 AC: 37 AN: 4866

South Asian (SAS) AF: 0.319 AC: 1476 AN: 4634

European-Finnish (FIN) AF: 0.604 AC: 5617 AN: 9294

Middle Eastern (MID) AF: 0.628 AC: 177 AN: 282

European-Non Finnish (NFE) AF: 0.640 AC: 43104 AN: 67402

Other (OTH) AF: 0.523 AC: 1053 AN: 2014

Alfa AF: 0.578 Hom.: 114811

Bravo AF: 0.456

Asia WGS AF: 0.159 AC: 556 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.58
PhyloP100		0.030
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: rs11755724; hg19: chr6-7118990;