Genetic Variant GTF2H4:c.958+64C>T (chr6-30912210-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.958+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,603,026 control chromosomes in the GnomAD database, including 12,997 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 0.075 ( 609 hom., cov: 31)

Exomes 𝑓: 0.12 ( 12388 hom. )

Consequence

GTF2H4
NM_001517.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

33 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 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.958+64C>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.958+64C>T	intron	N/A	ENSP00000259895.4	Q92759-1
GTF2H4	ENST00000376316.5	TSL:5	c.958+64C>T	intron	N/A	ENSP00000365493.2	Q92759-1
GTF2H4	ENST00000903713.1		c.958+64C>T	intron	N/A	ENSP00000573772.1

Frequencies

GnomAD3 genomes

AF:

0.0745

AC:

11326

AN:

151968

Hom.:

609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.146

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.0536

Gnomad FIN

AF:

0.0703

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.0533

GnomAD4 exome

AF:

0.119

AC:

173109

AN:

1450940

Hom.:

12388

Cov.:

AF XY:

0.118

AC XY:

85044

AN XY:

721056

show subpopulations

African (AFR)

AF:

0.0328

AC:

1091

AN:

33292

American (AMR)

AF:

0.0224

AC:

993

AN:

44384

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

1127

AN:

25584

East Asian (EAS)

AF:

0.00104

AC:

AN:

39606

South Asian (SAS)

AF:

0.0695

AC:

5926

AN:

85240

European-Finnish (FIN)

AF:

0.0746

AC:

3859

AN:

51730

Middle Eastern (MID)

AF:

0.0390

AC:

223

AN:

5722

European-Non Finnish (NFE)

AF:

0.139

AC:

153709

AN:

1105346

Other (OTH)

AF:

0.102

AC:

6140

AN:

60036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8131

16262

24393

32524

40655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5598

11196

16794

22392

27990

<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:

0.0746

AC:

11351

AN:

152086

Hom.:

609

Cov.:

AF XY:

0.0695

AC XY:

5167

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0331

AC:

1374

AN:

41488

American (AMR)

AF:

0.0293

AC:

448

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0444

AC:

154

AN:

3468

East Asian (EAS)

AF:

0.00406

AC:

AN:

5178

South Asian (SAS)

AF:

0.0547

AC:

263

AN:

4810

European-Finnish (FIN)

AF:

0.0703

AC:

745

AN:

10596

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8098

AN:

67948

Other (OTH)

AF:

0.0527

AC:

111

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

517

1034

1551

2068

2585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.106

Hom.:

4047

Bravo

AF:

0.0694

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.2

(source)

DANN

Benign

0.54

PhyloP100

-0.066

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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