Genetic Variant GTF2IRD2B:p.Val152Ala (chr7-75123232-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001003795.3(GTF2IRD2B):c.455T>C(p.Val152Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,340,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

GTF2IRD2B
NM_001003795.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Publications

0 publications found

Variant links:

Genes affected

GTF2IRD2B (HGNC:33125): (GTF2I repeat domain containing 2B) This gene encodes a glycosylated phosphoprotein with a leucine zipper motif, two helix-loop-helix motifs (I repeats) that are similar to domains found in the TFII-I family of transcription factors, one CHARLIE8 transposable element-like sequence, and a BED zinc finger. This gene lies within a region that is deleted in Williams-Beuren syndrome. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GTF2IRD2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26428542).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003795.3. 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
	GTF2IRD2B	NM_001003795.3	MANE Select	c.455T>C	p.Val152Ala	missense	Exon 5 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.941T>C	p.Val314Ala	missense	Exon 5 of 16	NP_001355231.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF2IRD2B	ENST00000472837.7	TSL:1 MANE Select	c.455T>C	p.Val152Ala	missense	Exon 5 of 16	ENSP00000480524.1	Q6EKJ0-1
GTF2IRD2B	ENST00000619142.4	TSL:1	c.455T>C	p.Val152Ala	missense	Exon 5 of 16	ENSP00000480037.1	A0A087WW90
GTF2IRD2B	ENST00000418185.6	TSL:1	n.455T>C		non_coding_transcript_exon	Exon 5 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000998

AC:

AN:

200358

AF XY:

0.0000181

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000211

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1340608

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28088

American (AMR)

AF:

0.00

AC:

AN:

32576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23612

East Asian (EAS)

AF:

0.00

AC:

AN:

38894

South Asian (SAS)

AF:

0.00

AC:

AN:

77658

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3782

European-Non Finnish (NFE)

AF:

0.00000291

AC:

AN:

1029336

Other (OTH)

AF:

0.00

AC:

AN:

55646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.028

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.69

M_CAP

Benign

0.0057

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PhyloP100

3.5

PrimateAI

Benign

0.46

Sift4G

Uncertain

0.0080

Polyphen

0.0060

Vest4

0.24

MutPred

0.76

Gain of disorder (P = 0.0391)

MVP

0.040

ClinPred

0.050

GERP RS

2.9

Varity_R

0.094

gMVP

0.10

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over