dbSNP rs2267831: GTF2IRD1:c.-1493G>C (chr7-74506190-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000476977.5(GTF2IRD1):c.-1493G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,200 control chromosomes in the GnomAD database, including 2,033 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 0.10 ( 2033 hom., cov: 32)

Exomes 𝑓: 0.036 ( 0 hom. )

Consequence

GTF2IRD1
ENST00000476977.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.152

Publications

3 publications found

Variant links:

Genes affected

GTF2IRD1 (HGNC:4661): (GTF2I repeat domain containing 1) The protein encoded by this gene contains five GTF2I-like repeats and each repeat possesses a potential helix-loop-helix (HLH) motif. It may have the ability to interact with other HLH-proteins and function as a transcription factor or as a positive transcriptional regulator under the control of Retinoblastoma protein. This gene plays a role in craniofacial and cognitive development and mutations have been associated with Williams-Beuren syndrome, a multisystem developmental disorder caused by deletion of multiple genes at 7q11.23. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

GTF2IRD1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

GTF2IRD1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000476977.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000476977.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2IRD1	NM_005685.4	MANE Select	c.-6-1885G>C	intron	N/A	NP_005676.3
GTF2IRD1	NM_001199207.2		c.-6-1885G>C	intron	N/A	NP_001186136.1	Q9UHL9-3
GTF2IRD1	NM_001410888.1		c.-6-1885G>C	intron	N/A	NP_001397817.1	E9PFE2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2IRD1	ENST00000476977.5	TSL:1	c.-1493G>C	5_prime_UTR	Exon 1 of 26	ENSP00000418383.1	E9PFE2
GTF2IRD1	ENST00000424337.7	TSL:1 MANE Select	c.-6-1885G>C	intron	N/A	ENSP00000408477.2	Q9UHL9-2
GTF2IRD1	ENST00000455841.6	TSL:1	c.-6-1885G>C	intron	N/A	ENSP00000397566.2	Q9UHL9-3

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15798

AN:

152054

Hom.:

2027

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.387

Gnomad SAS

AF:

0.0475

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00434

Gnomad OTH

AF:

0.0789

GnomAD4 exome

AF:

0.0357

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 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: 0.275

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

AF:

0.104

AC:

15828

AN:

152172

Hom.:

2033

Cov.:

AF XY:

0.105

AC XY:

7811

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.270

AC:

11217

AN:

41496

American (AMR)

AF:

0.112

AC:

1720

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00576

AC:

AN:

3472

East Asian (EAS)

AF:

0.388

AC:

1994

AN:

5142

South Asian (SAS)

AF:

0.0477

AC:

230

AN:

4822

European-Finnish (FIN)

AF:

0.0172

AC:

183

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00434

AC:

295

AN:

68010

Other (OTH)

AF:

0.0781

AC:

165

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

600

1199

1799

2398

2998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

312

468

624

780

<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:

0.0547

Hom.:

120

Bravo

AF:

0.118

Asia WGS

AF:

0.208

AC:

723

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

1.8

(source)

DANN

Benign

0.58

PhyloP100

-0.15

PromoterAI

-0.010

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over