Variant chr7-74515496-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_005685.4(GTF2IRD1):c.321C>T(p.Gly107Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,612,204 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.014 ( 216 hom. )

Consequence

GTF2IRD1
NM_005685.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.25

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 links:

GTF2IRD1 (HGNC:):

GTF2IRD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-74515496-C-T is Benign according to our data. Variant chr7-74515496-C-T is described in ClinVar as [Benign]. Clinvar id is 3387882.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2048/152236) while in subpopulation NFE AF= 0.0175 (1188/68008). AF 95% confidence interval is 0.0166. There are 21 homozygotes in gnomad4. There are 1098 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2048 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2IRD1	NM_005685.4 linkuse as main transcript	c.321C>T	p.Gly107Gly	synonymous_variant	4/27	ENST00000424337.7	NP_005676.3	Q9UHL9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2IRD1	ENST00000424337.7 linkuse as main transcript	c.321C>T	p.Gly107Gly	synonymous_variant	4/27	1	NM_005685.4	ENSP00000408477.2		Q9UHL9-2

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2046

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00885

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0446

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0175

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0141

AC:

3485

AN:

247542

Hom.:

AF XY:

0.0140

AC XY:

1874

AN XY:

134070

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00572

Gnomad ASJ exome

AF:

0.0109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00541

Gnomad FIN exome

AF:

0.0400

Gnomad NFE exome

AF:

0.0183

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0140

AC:

20468

AN:

1459968

Hom.:

216

Cov.:

AF XY:

0.0140

AC XY:

10189

AN XY:

726130

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00631

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00563

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.0146

Gnomad4 OTH exome

AF:

0.0129

GnomAD4 genome

AF:

0.0135

AC:

2048

AN:

152236

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1098

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.00883

Gnomad4 ASJ

AF:

0.00981

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00685

Gnomad4 FIN

AF:

0.0446

Gnomad4 NFE

AF:

0.0175

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0150

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00318

AC:

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 submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2024

GTF2IRD1: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.6

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over