NM_032999.4:c.-5-4320C>G

Variant names:

• chr7-74684804-C-G
• rs2527367
• NM_032999.4:c.-5-4320C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032999.4(GTF2I):​c.-5-4320C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: GTF2I NM_032999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 7 publications found

Genes affected

GTF2I (HGNC:4659): (general transcription factor IIi) This gene encodes a phosphoprotein containing six characteristic repeat motifs. The encoded protein binds to the initiator element (Inr) and E-box element in promoters and functions as a regulator of transcription. This locus, along with several other neighboring genes, is deleted in Williams-Beuren syndrome. There are many closely related genes and pseudogenes for this gene on chromosome 7. This gene also has pseudogenes on chromosomes 9, 13, and 21. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2013]

GTF2I-AS1 (HGNC:55572): (GTF2I antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032999.4. 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
	GTF2I	NM_032999.4	MANE Select	c.-5-4320C>G		intron	N/A	NP_127492.1	P78347-1
	GTF2I	NM_033000.4		c.-5-4320C>G		intron	N/A	NP_127493.1	P78347-3
	GTF2I	NM_033001.4		c.-5-4320C>G		intron	N/A	NP_127494.1	P78347-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2I	ENST00000573035.6	TSL:1 MANE Select	c.-5-4320C>G		intron	N/A	ENSP00000460070.1	P78347-1
	GTF2I	ENST00000614986.4	TSL:1	c.-5-4320C>G		intron	N/A	ENSP00000484526.1	P78347-3
	GTF2I	ENST00000621734.4	TSL:1	c.-5-4320C>G		intron	N/A	ENSP00000482476.1	P78347-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.41
PhyloP100		-0.098
PromoterAI		0.019	Neutral

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

Other links and lift over

dbSNP: rs2527367; hg19: chr7-74099138;