7-74797820-G-A

Variant names:

• chr7-74797820-G-A
• rs145968247
• NM_173537.5:c.1692C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173537.5(GTF2IRD2):​c.1692C>T​(p.Ala564Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: GTF2IRD2 NM_173537.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.302
• Publications: 1 publications found

Genes affected

GTF2IRD2 (HGNC:30775): (GTF2I repeat domain containing 2) This gene is one of several closely related genes on chromosome 7 encoding proteins containing helix-loop-helix motifs. These proteins may function as regulators of transcription. The encoded protein is unique in that its C-terminus is derived from CHARLIE8 transposable element sequence. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, and loss of this locus may contribute to the cognitive phenotypes observed in this disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ENSG00000289346 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 7-74797820-G-A is Benign according to our data. Variant chr7-74797820-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3770528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.302 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173537.5. 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
	GTF2IRD2	NM_173537.5	MANE Select	c.1692C>T	p.Ala564Ala	synonymous	Exon 16 of 16	NP_775808.4
	GTF2IRD2	NM_001368300.2		c.2178C>T	p.Ala726Ala	synonymous	Exon 17 of 17	NP_001355229.1	A0A494C0I1
	GTF2IRD2	NM_001388079.1		c.1707C>T	p.Ala569Ala	synonymous	Exon 16 of 16	NP_001375008.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2IRD2	ENST00000451013.7	TSL:1 MANE Select	c.1692C>T	p.Ala564Ala	synonymous	Exon 16 of 16	ENSP00000406723.3	Q86UP8-1
	ENSG00000289346	ENST00000625377.3	TSL:5	c.1692C>T	p.Ala564Ala	synonymous	Exon 23 of 23	ENSP00000486581.2
	GTF2IRD2	ENST00000651129.1		c.2178C>T	p.Ala726Ala	synonymous	Exon 17 of 17	ENSP00000498563.1	A0A494C0I1

Frequencies

GnomAD3 genomes AF: 0.000753 AC: 96 AN: 127574 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000278

Gnomad AMI AF: 0.00123

Gnomad AMR AF: 0.0000866

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000479

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000679 AC: 119 AN: 175166 AF XY: 0.000745

Gnomad AFR exome AF: 0.000487

Gnomad AMR exome AF: 0.0000813

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000176

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.000443

GnomAD4 exome AF: 0.00125 AC: 1421 AN: 1141180 Hom.: 4 Cov.: 19 AF XY: 0.00126 AC XY: 726 AN XY: 574280

African (AFR) AF: 0.000391 AC: 10 AN: 25594

American (AMR) AF: 0.000112 AC: 4 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22204

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35494

South Asian (SAS) AF: 0.00 AC: 0 AN: 72812

European-Finnish (FIN) AF: 0.000298 AC: 15 AN: 50288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5122

European-Non Finnish (NFE) AF: 0.00160 AC: 1354 AN: 844790

Other (OTH) AF: 0.000751 AC: 37 AN: 49260

GnomAD4 genome AF: 0.000752 AC: 96 AN: 127668 Hom.: 0 Cov.: 16 AF XY: 0.000594 AC XY: 36 AN XY: 60600

African (AFR) AF: 0.000277 AC: 9 AN: 32514

American (AMR) AF: 0.0000865 AC: 1 AN: 11562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3190

East Asian (EAS) AF: 0.00 AC: 0 AN: 4136

South Asian (SAS) AF: 0.00 AC: 0 AN: 3434

European-Finnish (FIN) AF: 0.000479 AC: 4 AN: 8348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00131 AC: 81 AN: 61730

Other (OTH) AF: 0.00 AC: 0 AN: 1662

Alfa AF: 0.000857 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.2
DANN	Benign	0.89
PhyloP100		0.30
Mutation Taster		=99/1	polymorphism

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: rs145968247; hg19: chr7-74212159;