dbSNP rs2340693: GTF2H3:c.365-553A>G (chr12-123650441-A-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_001516.5(GTF2H3):c.365-553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 153,418 control chromosomes in the GnomAD database, including 2,850 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 0.12 ( 2850 hom., cov: 32)

Exomes 𝑓: 0.018 ( 0 hom. )

Consequence

GTF2H3
NM_001516.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.379

Publications

5 publications found

Variant links:

Genes affected

GTF2H3 (HGNC:4657): (general transcription factor IIH subunit 3) This gene encodes a member of the TFB4 family. The encoded protein is a subunit of the core-TFIIH basal transcription factor and localizes to the nucleus. The encoded protein is involved in RNA transcription by RNA polymerase II and nucleotide excision repair and associates with the Cdk-activating kinase complex. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 14. [provided by RefSeq, Dec 2012]

GTF2H3 links:

ENSG00000279953 (HGNC:):

ENSG00000279953 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001516.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2H3	NM_001516.5	MANE Select	c.365-553A>G	intron	N/A	NP_001507.2
GTF2H3	NM_001271867.2		c.242-553A>G	intron	N/A	NP_001258796.1	Q13889-2
GTF2H3	NM_001271866.2		c.365-553A>G	intron	N/A	NP_001258795.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GTF2H3	ENST00000543341.7	TSL:1 MANE Select	c.365-553A>G	intron	N/A	ENSP00000445162.1	Q13889-1
GTF2H3	ENST00000228955.11	TSL:2	c.242-553A>G	intron	N/A	ENSP00000228955.7	Q13889-2
GTF2H3	ENST00000536375.5	TSL:5	c.365-553A>G	intron	N/A	ENSP00000441894.1	F5GWD3

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18210

AN:

152056

Hom.:

2843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.363

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0560

Gnomad ASJ

AF:

0.0514

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.0515

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0231

Gnomad OTH

AF:

0.0959

GnomAD4 exome

AF:

0.0185

AC:

AN:

1244

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

AN XY:

676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0211

AC:

AN:

142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0233

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0195

AC:

AN:

872

Other (OTH)

AF:

0.0185

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.560

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.120

AC:

18265

AN:

152174

Hom.:

2850

Cov.:

AF XY:

0.116

AC XY:

8635

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.363

AC:

15041

AN:

41446

American (AMR)

AF:

0.0559

AC:

855

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

178

AN:

3466

East Asian (EAS)

AF:

0.00347

AC:

AN:

5192

South Asian (SAS)

AF:

0.0519

AC:

251

AN:

4834

European-Finnish (FIN)

AF:

0.00706

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0231

AC:

1570

AN:

68016

Other (OTH)

AF:

0.0944

AC:

199

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

615

1230

1844

2459

3074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<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:

0.0645

Hom.:

2246

Bravo

AF:

0.135

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.2

(source)

DANN

Benign

0.62

PhyloP100

0.38

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