6-7240344-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001003699.4(RREB1):c.3809-94A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 922,630 control chromosomes in the GnomAD database, including 54,438 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 0.34 (8868 hom., cov: 30)
  • Exomes 𝑓: 0.34 (45570 hom.)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RREB1	NM_001003699.4	c.3809-94A>T		intron_variant		ENST00000379938.7
RREB1	NM_001003698.4	c.3809-6080A>T		intron_variant
RREB1	NM_001003700.2	c.3809-94A>T		intron_variant
RREB1	NM_001168344.2	c.3809-6080A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RREB1	ENST00000379938.7	c.3809-94A>T		intron_variant		1	NM_001003699.4	P1
RREB1	ENST00000334984.10	c.3809-94A>T		intron_variant		1
RREB1	ENST00000349384.10	c.3809-6080A>T		intron_variant		1
RREB1	ENST00000379933.7	c.3809-6080A>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51033 AN: 151488 Hom.: 8870 Cov.: 30

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.337 AC: 260115 AN: 771026 Hom.: 45570 AF XY: 0.338 AC XY: 132234 AN XY: 390676

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.337 AC: 51048 AN: 151604 Hom.: 8868 Cov.: 30 AF XY: 0.341 AC XY: 25229 AN XY: 74080

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.319

Alfa AF: 0.330 Hom.: 1071

Bravo AF: 0.332

Asia WGS AF: 0.406 AC: 1409 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.76

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: rs2714337; hg19: chr6-7240577;