rs4960294

Positions:

• chr6-7198740-A-C

Variant summary

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

The NM_001003699.4(RREB1):​c.425+9418A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,078 control chromosomes in the GnomAD database, including 8,966 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 (8966 hom., cov: 32)
• Consequence: RREB1 NM_001003699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RREB1	NM_001003699.4	c.425+9418A>C		intron_variant		ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4	c.425+9418A>C		intron_variant			NP_001003698.1
RREB1	NM_001168344.2	c.425+9418A>C		intron_variant			NP_001161816.1
RREB1	NM_001003700.2	c.425+9418A>C		intron_variant			NP_001003700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7	c.425+9418A>C		intron_variant		1	NM_001003699.4	ENSP00000369270.2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51500 AN: 151960 Hom.: 8966 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.339 AC: 51502 AN: 152078 Hom.: 8966 Cov.: 32 AF XY: 0.336 AC XY: 24973 AN XY: 74350

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.342

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.360

Alfa AF: 0.360 Hom.: 2705

Bravo AF: 0.339

Asia WGS AF: 0.228 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.72

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: rs4960294; hg19: chr6-7198973;