Genetic Variant GTF2H4:c.560+51C>T (chr6-30910992-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001517.5(GTF2H4):c.560+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,464,722 control chromosomes in the GnomAD database, including 46,930 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 0.26 ( 6017 hom., cov: 31)

Exomes 𝑓: 0.22 ( 40913 hom. )

Consequence

GTF2H4
NM_001517.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

17 publications found

Variant links:

Genes affected

GTF2H4 (HGNC:4658): (general transcription factor IIH subunit 4) Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H4 links:

ENSG00000288473 (HGNC:):

ENSG00000288473 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001517.5. 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
	GTF2H4	NM_001517.5	MANE Select	c.560+51C>T		intron	N/A	NP_001508.1	A0A1U9X7S4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2H4	ENST00000259895.9	TSL:1 MANE Select	c.560+51C>T	intron	N/A	ENSP00000259895.4	Q92759-1
GTF2H4	ENST00000376316.5	TSL:5	c.560+51C>T	intron	N/A	ENSP00000365493.2	Q92759-1
GTF2H4	ENST00000903713.1		c.560+51C>T	intron	N/A	ENSP00000573772.1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39409

AN:

151654

Hom.:

6003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.607

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.226

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.255

GnomAD2 exomes

AF:

0.315

AC:

57219

AN:

181890

AF XY:

0.316

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.588

Gnomad FIN exome

AF:

0.256

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.222

AC:

291098

AN:

1312950

Hom.:

40913

Cov.:

AF XY:

0.229

AC XY:

149880

AN XY:

655610

show subpopulations

African (AFR)

AF:

0.257

AC:

7891

AN:

30690

American (AMR)

AF:

0.453

AC:

16884

AN:

37236

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

6525

AN:

24650

East Asian (EAS)

AF:

0.578

AC:

21547

AN:

37280

South Asian (SAS)

AF:

0.469

AC:

37614

AN:

80184

European-Finnish (FIN)

AF:

0.259

AC:

12048

AN:

46584

Middle Eastern (MID)

AF:

0.275

AC:

1499

AN:

5442

European-Non Finnish (NFE)

AF:

0.173

AC:

172627

AN:

995610

Other (OTH)

AF:

0.262

AC:

14463

AN:

55274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

11643

23286

34930

46573

58216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6172

12344

18516

24688

30860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.260

AC:

39446

AN:

151772

Hom.:

6017

Cov.:

AF XY:

0.270

AC XY:

20041

AN XY:

74150

show subpopulations

African (AFR)

AF:

0.271

AC:

11215

AN:

41352

American (AMR)

AF:

0.367

AC:

5597

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

885

AN:

3466

East Asian (EAS)

AF:

0.608

AC:

3121

AN:

5134

South Asian (SAS)

AF:

0.509

AC:

2449

AN:

4808

European-Finnish (FIN)

AF:

0.256

AC:

2690

AN:

10504

Middle Eastern (MID)

AF:

0.226

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.185

AC:

12596

AN:

67944

Other (OTH)

AF:

0.262

AC:

554

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1384

2768

4153

5537

6921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

410

820

1230

1640

2050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

5400

Bravo

AF:

0.266

Asia WGS

AF:

0.551

AC:

1912

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.8

(source)

DANN

Benign

0.60

PhyloP100

-0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over