7-74684804-C-T

Variant names:

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

Variant summary

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

The NM_032999.4(GTF2I):​c.-5-4320C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,038 control chromosomes in the GnomAD database, including 29,202 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 0.60 (29193 hom., cov: 32)
  • Exomes 𝑓: 0.78 (9 hom.)
• 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: 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 = 0.878 is higher than 0.05.

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>T		intron	N/A	NP_127492.1	P78347-1
	GTF2I	NM_033000.4		c.-5-4320C>T		intron	N/A	NP_127493.1	P78347-3
	GTF2I	NM_033001.4		c.-5-4320C>T		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>T		intron	N/A	ENSP00000460070.1	P78347-1
	GTF2I	ENST00000614986.4	TSL:1	c.-5-4320C>T		intron	N/A	ENSP00000484526.1	P78347-3
	GTF2I	ENST00000621734.4	TSL:1	c.-5-4320C>T		intron	N/A	ENSP00000482476.1	P78347-4

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90517 AN: 151888 Hom.: 29184 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.687

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.643

GnomAD4 exome AF: 0.781 AC: 25 AN: 32 Hom.: 9 Cov.: 0 AF XY: 0.708 AC XY: 17 AN XY: 24

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.792 AC: 19 AN: 24

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.596 AC: 90558 AN: 152006 Hom.: 29193 Cov.: 32 AF XY: 0.603 AC XY: 44826 AN XY: 74306

African (AFR) AF: 0.339 AC: 14067 AN: 41436

American (AMR) AF: 0.712 AC: 10889 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 2385 AN: 3472

East Asian (EAS) AF: 0.900 AC: 4632 AN: 5148

South Asian (SAS) AF: 0.759 AC: 3664 AN: 4826

European-Finnish (FIN) AF: 0.722 AC: 7618 AN: 10558

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45006 AN: 67970

Other (OTH) AF: 0.636 AC: 1340 AN: 2106

Alfa AF: 0.641 Hom.: 14084

Bravo AF: 0.585

Asia WGS AF: 0.743 AC: 2585 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	4.8
DANN	Benign	0.44
PhyloP100		-0.098
PromoterAI		-0.0082	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;