rs4717901

Variant names:

• chr7-74602653-A-C
• rs4717901
• NM_005685.4:c.*220A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005685.4(GTF2IRD1):​c.*220A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 432,214 control chromosomes in the GnomAD database, including 917 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 0.038 (271 hom., cov: 32)
  • Exomes 𝑓: 0.047 (646 hom.)
• Consequence: GTF2IRD1 NM_005685.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 7 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005685.4. 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
	GTF2IRD1	NM_005685.4	MANE Select	c.*220A>C		downstream_gene	N/A	NP_005676.3
	GTF2IRD1	NM_001199207.2		c.*220A>C		downstream_gene	N/A	NP_001186136.1	Q9UHL9-3
	GTF2IRD1	NM_016328.3		c.*220A>C		downstream_gene	N/A	NP_057412.1	Q9UHL9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD1	ENST00000424337.7	TSL:1 MANE Select	c.*220A>C		downstream_gene	N/A	ENSP00000408477.2	Q9UHL9-2
	GTF2IRD1	ENST00000455841.6	TSL:1	c.*220A>C		downstream_gene	N/A	ENSP00000397566.2	Q9UHL9-3
	GTF2IRD1	ENST00000476977.5	TSL:1	c.*1356A>C		downstream_gene	N/A	ENSP00000418383.1	E9PFE2

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5743 AN: 151164 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.0705

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0431

GnomAD4 exome AF: 0.0473 AC: 13283 AN: 280990 Hom.: 646 Cov.: 4 AF XY: 0.0486 AC XY: 7278 AN XY: 149840

African (AFR) AF: 0.00785 AC: 62 AN: 7898

American (AMR) AF: 0.118 AC: 1385 AN: 11748

Ashkenazi Jewish (ASJ) AF: 0.0388 AC: 345 AN: 8886

East Asian (EAS) AF: 0.171 AC: 3337 AN: 19494

South Asian (SAS) AF: 0.0742 AC: 2092 AN: 28200

European-Finnish (FIN) AF: 0.0367 AC: 539 AN: 14682

Middle Eastern (MID) AF: 0.0373 AC: 45 AN: 1208

European-Non Finnish (NFE) AF: 0.0278 AC: 4801 AN: 172792

Other (OTH) AF: 0.0421 AC: 677 AN: 16082

GnomAD4 genome AF: 0.0381 AC: 5757 AN: 151224 Hom.: 271 Cov.: 32 AF XY: 0.0421 AC XY: 3108 AN XY: 73760

African (AFR) AF: 0.00602 AC: 248 AN: 41178

American (AMR) AF: 0.102 AC: 1550 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.193 AC: 993 AN: 5150

South Asian (SAS) AF: 0.0709 AC: 339 AN: 4784

European-Finnish (FIN) AF: 0.0510 AC: 523 AN: 10258

Middle Eastern (MID) AF: 0.0246 AC: 7 AN: 284

European-Non Finnish (NFE) AF: 0.0274 AC: 1860 AN: 67940

Other (OTH) AF: 0.0433 AC: 90 AN: 2078

Alfa AF: 0.0279 Hom.: 60

Bravo AF: 0.0404

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.51
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4717901; hg19: chr7-74016979;