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GeneBe

7-74518164-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_005685.4(GTF2IRD1):c.447G>T(p.Val149=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00903 in 1,600,966 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0075 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0092 ( 78 hom. )

Consequence

GTF2IRD1
NM_005685.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.10
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-74518164-G-T is Benign according to our data. Variant chr7-74518164-G-T is described in ClinVar as [Benign]. Clinvar id is 2657595.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1136 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTF2IRD1NM_005685.4 linkuse as main transcriptc.447G>T p.Val149= synonymous_variant 5/27 ENST00000424337.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTF2IRD1ENST00000424337.7 linkuse as main transcriptc.447G>T p.Val149= synonymous_variant 5/271 NM_005685.4 P1Q9UHL9-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00746
AC:
1136
AN:
152230
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00345
Gnomad AMI
AF:
0.0308
Gnomad AMR
AF:
0.00818
Gnomad ASJ
AF:
0.00375
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00301
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0113
Gnomad OTH
AF:
0.00860
GnomAD3 exomes
AF:
0.00672
AC:
1602
AN:
238554
Hom.:
3
AF XY:
0.00641
AC XY:
836
AN XY:
130394
show subpopulations
Gnomad AFR exome
AF:
0.00321
Gnomad AMR exome
AF:
0.00556
Gnomad ASJ exome
AF:
0.00354
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00114
Gnomad FIN exome
AF:
0.00464
Gnomad NFE exome
AF:
0.0110
Gnomad OTH exome
AF:
0.00563
GnomAD4 exome
AF:
0.00920
AC:
13323
AN:
1448618
Hom.:
78
Cov.:
31
AF XY:
0.00898
AC XY:
6456
AN XY:
718686
show subpopulations
Gnomad4 AFR exome
AF:
0.00356
Gnomad4 AMR exome
AF:
0.00553
Gnomad4 ASJ exome
AF:
0.00348
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00135
Gnomad4 FIN exome
AF:
0.00512
Gnomad4 NFE exome
AF:
0.0109
Gnomad4 OTH exome
AF:
0.00728
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00746
AC:
1136
AN:
152348
Hom.:
4
Cov.:
32
AF XY:
0.00724
AC XY:
539
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.00344
Gnomad4 AMR
AF:
0.00816
Gnomad4 ASJ
AF:
0.00375
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00301
Gnomad4 NFE
AF:
0.0113
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.0102
Hom.:
2
Bravo
AF:
0.00858
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMay 01, 2023GTF2IRD1: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
6.5
Dann
Benign
0.83
RBP_binding_hub_radar
1.0
RBP_regulation_power_radar
2.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs145535993; hg19: chr7-73932494; COSMIC: COSV99735937; API