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7-74508119-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_005685.4(GTF2IRD1):c.39C>T(p.Asn13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00086 in 1,610,872 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00085 ( 4 hom. )

Consequence

GTF2IRD1
NM_005685.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0540
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 -15 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=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-74508119-C-T is Benign according to our data. Variant chr7-74508119-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 773212.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.054 with no splicing effect.
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 151 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTF2IRD1NM_005685.4 linkuse as main transcriptc.39C>T p.Asn13= synonymous_variant 2/27 ENST00000424337.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTF2IRD1ENST00000424337.7 linkuse as main transcriptc.39C>T p.Asn13= synonymous_variant 2/271 NM_005685.4 P1Q9UHL9-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000992
AC:
151
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00125
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00115
AC:
286
AN:
248158
Hom.:
1
AF XY:
0.00124
AC XY:
167
AN XY:
134434
show subpopulations
Gnomad AFR exome
AF:
0.000370
Gnomad AMR exome
AF:
0.00145
Gnomad ASJ exome
AF:
0.00339
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000261
Gnomad FIN exome
AF:
0.000106
Gnomad NFE exome
AF:
0.00155
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.000845
AC:
1233
AN:
1458584
Hom.:
4
Cov.:
31
AF XY:
0.000876
AC XY:
636
AN XY:
725776
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00136
Gnomad4 ASJ exome
AF:
0.00387
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.000139
Gnomad4 NFE exome
AF:
0.000854
Gnomad4 OTH exome
AF:
0.00121
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000998
AC:
152
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.000954
AC XY:
71
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.00125
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00149
Hom.:
0
Bravo
AF:
0.00113
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00202
EpiControl
AF:
0.00219

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023GTF2IRD1: BP4, BP7 -
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
13
Dann
Benign
0.83
RBP_binding_hub_radar
0.0
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: rs151198189; hg19: chr7-73922449; COSMIC: COSV56086990; API