rs4717901

chr7-74602653-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 7-74602653-A-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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF2IRD1	NM_005685.4			downstream_gene_variant		ENST00000424337.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF2IRD1	ENST00000424337.7			downstream_gene_variant		1	NM_005685.4	P1
GTF2IRD1	ENST00000455841.6			downstream_gene_variant		1

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

Gnomad4 AFR exome AF: 0.00785

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.0388

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.0742

Gnomad4 FIN exome AF: 0.0367

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.0421

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

Gnomad4 AFR AF: 0.00602

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.0709

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0274

Gnomad4 OTH AF: 0.0433

Alfa AF: 0.0278 Hom.: 16

Bravo AF: 0.0404

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.1
Dann	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4717901; hg19: chr7-74016979;