NM_001003699.4:c.87G>T

Variant names:

• chr6-7181998-G-T
• rs116604236
• NM_001003699.4:c.87G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003699.4(RREB1):​c.87G>T​(p.Lys29Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K29K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RREB1 NM_001003699.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• RASopathy

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• 22q11.2 deletion syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09431258).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RREB1	NM_001003699.4	MANE Select	c.87G>T	p.Lys29Asn	missense	Exon 4 of 13	NP_001003699.1	Q92766-2
	RREB1	NM_001003698.4		c.87G>T	p.Lys29Asn	missense	Exon 4 of 12	NP_001003698.1	Q92766-1
	RREB1	NM_001168344.2		c.87G>T	p.Lys29Asn	missense	Exon 4 of 12	NP_001161816.1	Q92766-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RREB1	ENST00000379938.7	TSL:1 MANE Select	c.87G>T	p.Lys29Asn	missense	Exon 4 of 13	ENSP00000369270.2	Q92766-2
	RREB1	ENST00000349384.10	TSL:1	c.87G>T	p.Lys29Asn	missense	Exon 4 of 12	ENSP00000305560.10	Q92766-1
	RREB1	ENST00000379933.7	TSL:1	c.87G>T	p.Lys29Asn	missense	Exon 4 of 12	ENSP00000369265.3	Q92766-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.67	N
PhyloP100		2.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.029
Sift	Benign	0.21	T
Sift4G	Uncertain	0.055	T
Polyphen		0.0040	B
Vest4		0.32
MutPred		0.26		Loss of ubiquitination at K29 (P = 0.0037)
MVP		0.33
MPC		0.62
ClinPred		0.097	T
GERP RS		3.0
Varity_R		0.041
gMVP		0.42
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs116604236; hg19: chr6-7182231;