rs2714357

Variant names:

• chr6-7225762-G-T
• rs2714357
• NM_001003699.4:c.708-705G>T

Variant summary

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

The NM_001003699.4(RREB1):​c.708-705G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,852 control chromosomes in the GnomAD database, including 13,824 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 0.40 (13824 hom., cov: 31)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) 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.708-705G>T		intron_variant	Intron 8 of 12	ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4	c.708-705G>T		intron_variant	Intron 8 of 11		NP_001003698.1
RREB1	NM_001168344.2	c.708-705G>T		intron_variant	Intron 8 of 11		NP_001161816.1
RREB1	NM_001003700.2	c.708-705G>T		intron_variant	Intron 8 of 11		NP_001003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7	c.708-705G>T		intron_variant	Intron 8 of 12	1	NM_001003699.4	ENSP00000369270.2

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60160 AN: 151734 Hom.: 13782 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.397 AC: 60264 AN: 151852 Hom.: 13824 Cov.: 31 AF XY: 0.391 AC XY: 29029 AN XY: 74208

African (AFR) AF: 0.641 AC: 26503 AN: 41358

American (AMR) AF: 0.248 AC: 3786 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.258 AC: 1330 AN: 5158

South Asian (SAS) AF: 0.201 AC: 968 AN: 4826

European-Finnish (FIN) AF: 0.387 AC: 4070 AN: 10528

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21443 AN: 67932

Other (OTH) AF: 0.360 AC: 759 AN: 2106

Alfa AF: 0.336 Hom.: 38944

Bravo AF: 0.397

Asia WGS AF: 0.238 AC: 827 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.43
PhyloP100		-0.69
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: rs2714357; hg19: chr6-7225995;