rs6931262

Positions:

• chr6-7217284-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001003699.4(RREB1):​c.707+5575C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,238 control chromosomes in the GnomAD database, including 1,606 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 0.10 (1606 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.197

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RREB1	NM_001003699.4	c.707+5575C>T		intron_variant		ENST00000379938.7
RREB1	NM_001003698.4	c.707+5575C>T		intron_variant
RREB1	NM_001003700.2	c.707+5575C>T		intron_variant
RREB1	NM_001168344.2	c.707+5575C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RREB1	ENST00000379938.7	c.707+5575C>T		intron_variant		1	NM_001003699.4	P1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15513 AN: 152072 Hom.: 1603 Cov.: 32

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0540

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0487

Gnomad FIN AF: 0.0394

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0824

GnomAD4 exome AF: 0.0208 AC: 1 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 1 AN XY: 26

Gnomad4 FIN exome AF: 0.0625

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.102 AC: 15542 AN: 152190 Hom.: 1606 Cov.: 32 AF XY: 0.101 AC XY: 7552 AN XY: 74410

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0539

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0487

Gnomad4 FIN AF: 0.0394

Gnomad4 NFE AF: 0.0297

Gnomad4 OTH AF: 0.0844

Alfa AF: 0.0439 Hom.: 513

Bravo AF: 0.109

Asia WGS AF: 0.117 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.55

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: rs6931262; hg19: chr6-7217517;