7-74506190-G-C

Position:

• chr7-74506190-G-C

Variant summary

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

The ENST00000476977(GTF2IRD1):​c.-1493G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,200 control chromosomes in the GnomAD database, including 2,033 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 0.10 (2033 hom., cov: 32)
  • Exomes 𝑓: 0.036 (0 hom.)
• Consequence: GTF2IRD1 ENST00000476977 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2IRD1	NM_005685.4	c.-6-1885G>C		intron_variant		ENST00000424337.7	NP_005676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2IRD1	ENST00000476977	c.-1493G>C		5_prime_UTR_variant	1/26	1		ENSP00000418383.1
GTF2IRD1	ENST00000424337.7	c.-6-1885G>C		intron_variant		1	NM_005685.4	ENSP00000408477.2
GTF2IRD1	ENST00000455841.6	c.-6-1885G>C		intron_variant		1		ENSP00000397566.2
GTF2IRD1	ENST00000265755.7	c.-6-1885G>C		intron_variant		1		ENSP00000265755.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15798 AN: 152054 Hom.: 2027 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00434

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0357 AC: 1 AN: 28 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.104 AC: 15828 AN: 152172 Hom.: 2033 Cov.: 32 AF XY: 0.105 AC XY: 7811 AN XY: 74390

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.00434

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0547 Hom.: 120

Bravo AF: 0.118

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2267831; hg19: chr7-73920520;