dbSNP rs4150563: GTF2H1:c.154+327T>G (chr11-18333555-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005316.4(GTF2H1):c.154+327T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 174,586 control chromosomes in the GnomAD database, including 2,845 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 0.15 ( 2326 hom., cov: 33)

Exomes 𝑓: 0.19 ( 519 hom. )

Consequence

GTF2H1
NM_005316.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

7 publications found

Variant links:

Genes affected

GTF2H1 (HGNC:4655): (general transcription factor IIH subunit 1) Enables thyroid hormone receptor binding activity. Involved in positive regulation of transcription, DNA-templated and transcription by RNA polymerase II. Located in nucleoplasm. Part of transcription factor TFIIH core complex and transcription factor TFIIH holo complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF2H1 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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005316.4. 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
	GTF2H1	NM_005316.4	MANE Select	c.154+327T>G		intron	N/A	NP_005307.1	P32780-1
	GTF2H1	NM_001142307.2		c.154+327T>G		intron	N/A	NP_001135779.1	P32780-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2H1	ENST00000265963.9	TSL:1 MANE Select	c.154+327T>G	intron	N/A	ENSP00000265963.4	P32780-1
GTF2H1	ENST00000928992.1		c.154+327T>G	intron	N/A	ENSP00000599051.1
GTF2H1	ENST00000453096.6	TSL:2	c.154+327T>G	intron	N/A	ENSP00000393638.2	P32780-1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23151

AN:

152126

Hom.:

2324

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0383

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.142

Gnomad ASJ

AF:

0.0748

Gnomad EAS

AF:

0.0391

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.214

Gnomad OTH

AF:

0.140

GnomAD4 exome

AF:

0.190

AC:

4237

AN:

22342

Hom.:

519

Cov.:

AF XY:

0.185

AC XY:

2116

AN XY:

11416

show subpopulations

African (AFR)

AF:

0.0270

AC:

AN:

704

American (AMR)

AF:

0.118

AC:

107

AN:

908

Ashkenazi Jewish (ASJ)

AF:

0.0839

AC:

AN:

822

East Asian (EAS)

AF:

0.0319

AC:

AN:

1346

South Asian (SAS)

AF:

0.116

AC:

140

AN:

1208

European-Finnish (FIN)

AF:

0.324

AC:

249

AN:

768

Middle Eastern (MID)

AF:

0.0980

AC:

AN:

102

European-Non Finnish (NFE)

AF:

0.221

AC:

3332

AN:

15078

Other (OTH)

AF:

0.191

AC:

268

AN:

1406

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

168

335

503

670

838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.152

AC:

23151

AN:

152244

Hom.:

2326

Cov.:

AF XY:

0.156

AC XY:

11621

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0382

AC:

1588

AN:

41570

American (AMR)

AF:

0.142

AC:

2168

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0748

AC:

259

AN:

3464

East Asian (EAS)

AF:

0.0391

AC:

203

AN:

5186

South Asian (SAS)

AF:

0.116

AC:

559

AN:

4832

European-Finnish (FIN)

AF:

0.310

AC:

3281

AN:

10576

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.214

AC:

14579

AN:

67998

Other (OTH)

AF:

0.139

AC:

294

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

994

1989

2983

3978

4972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.179

Hom.:

5664

Bravo

AF:

0.133

Asia WGS

AF:

0.0740

AC:

255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.6

(source)

DANN

Benign

0.72

PhyloP100

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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