rs41302867

Positions:

• chr6-7240643-G-A

Variant summary

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

The ENST00000379938.7(RREB1):​c.3973+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,584,576 control chromosomes in the GnomAD database, including 9,944 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 0.082 (687 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9257 hom.)
• Consequence: RREB1 ENST00000379938.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.951

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RREB1	NM_001003699.4	c.3973+41G>A		intron_variant		ENST00000379938.7	NP_001003699.1
RREB1	NM_001003698.4	c.3809-5781G>A		intron_variant			NP_001003698.1
RREB1	NM_001003700.2	c.3973+41G>A		intron_variant			NP_001003700.1
RREB1	NM_001168344.2	c.3809-5781G>A		intron_variant			NP_001161816.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RREB1	ENST00000379938.7	c.3973+41G>A		intron_variant		1	NM_001003699.4	ENSP00000369270	P1
RREB1	ENST00000334984.10	c.3973+41G>A		intron_variant		1		ENSP00000335574
RREB1	ENST00000349384.10	c.3809-5781G>A		intron_variant		1		ENSP00000305560
RREB1	ENST00000379933.7	c.3809-5781G>A		intron_variant		1		ENSP00000369265

Frequencies

GnomAD3 genomes AF: 0.0818 AC: 12451 AN: 152152 Hom.: 687 Cov.: 32

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0919

Gnomad ASJ AF: 0.0815

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0969

GnomAD3 exomes AF: 0.0849 AC: 20280 AN: 238992 Hom.: 1103 AF XY: 0.0874 AC XY: 11338 AN XY: 129704

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.0753

Gnomad EAS exome AF: 0.000338

Gnomad SAS exome AF: 0.0447

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.108 AC: 154909 AN: 1432306 Hom.: 9257 Cov.: 25 AF XY: 0.107 AC XY: 75913 AN XY: 711040

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.0747

Gnomad4 EAS exome AF: 0.000357

Gnomad4 SAS exome AF: 0.0455

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.122

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0817 AC: 12448 AN: 152270 Hom.: 687 Cov.: 32 AF XY: 0.0802 AC XY: 5975 AN XY: 74460

Gnomad4 AFR AF: 0.0220

Gnomad4 AMR AF: 0.0918

Gnomad4 ASJ AF: 0.0815

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.0955

Alfa AF: 0.100 Hom.: 179

Bravo AF: 0.0805

Asia WGS AF: 0.0200 AC: 69 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	1.7
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs41302867; hg19: chr6-7240876;