rs6597256

Positions:

• chr6-7207774-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RREB1	NM_001003699.4	c.426-3030G>A		intron_variant		ENST00000379938.7
RREB1	NM_001003698.4	c.426-3030G>A		intron_variant
RREB1	NM_001003700.2	c.426-3030G>A		intron_variant
RREB1	NM_001168344.2	c.426-3030G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RREB1	ENST00000379938.7	c.426-3030G>A		intron_variant		1	NM_001003699.4	P1

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

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.504

Alfa AF: 0.518 Hom.: 3546

Bravo AF: 0.555

Asia WGS AF: 0.747 AC: 2594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs6597256; hg19: chr6-7208007;