Genetic Variant GTF2IRD2B:p.Pro272Pro (chr7-75136795-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001003795.3(GTF2IRD2B):c.816G>C(p.Pro272Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts 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. P272P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 13)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTF2IRD2B
NM_001003795.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.905

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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.816G>C	p.Pro272Pro	synonymous	Exon 11 of 16	NP_001003795.1	Q6EKJ0-1
	GTF2IRD2B	NM_001368302.1		c.1302G>C	p.Pro434Pro	synonymous	Exon 11 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.816G>C	p.Pro272Pro	synonymous	Exon 11 of 16	ENSP00000480524.1	Q6EKJ0-1
GTF2IRD2B	ENST00000619142.4	TSL:1	c.816G>C	p.Pro272Pro	synonymous	Exon 11 of 16	ENSP00000480037.1	A0A087WW90
GTF2IRD2B	ENST00000418185.6	TSL:1	n.*91G>C		non_coding_transcript_exon	Exon 10 of 15	ENSP00000411454.3	Q6EKJ0-2

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

101022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000945

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

405436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

214728

African (AFR)

AF:

0.00

AC:

AN:

10232

American (AMR)

AF:

0.00

AC:

AN:

17414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12082

East Asian (EAS)

AF:

0.00

AC:

AN:

29182

South Asian (SAS)

AF:

0.00

AC:

AN:

43482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30176

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

238444

Other (OTH)

AF:

0.00

AC:

AN:

22842

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000198

AC:

AN:

101084

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

46522

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000941

AC:

AN:

21254

American (AMR)

AF:

0.00

AC:

AN:

9328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2798

East Asian (EAS)

AF:

0.00

AC:

AN:

4560

South Asian (SAS)

AF:

0.00

AC:

AN:

2920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51756

Other (OTH)

AF:

0.00

AC:

AN:

1298

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.49

(source)

DANN

Benign

0.54

PhyloP100

-0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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