dbSNP rs4150606: GTF2H1:c.837+415C>A (chr11-18342022-C-A) – 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.837+415C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 154,648 control chromosomes in the GnomAD database, including 18,909 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 0.46 ( 18504 hom., cov: 30)

Exomes 𝑓: 0.51 ( 405 hom. )

Consequence

GTF2H1
NM_005316.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0810

Publications

15 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:

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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.827 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.837+415C>A		intron	N/A	NP_005307.1	P32780-1
	GTF2H1	NM_001142307.2		c.837+415C>A		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.837+415C>A	intron	N/A	ENSP00000265963.4	P32780-1
GTF2H1	ENST00000928992.1		c.837+415C>A	intron	N/A	ENSP00000599051.1
GTF2H1	ENST00000453096.6	TSL:2	c.837+415C>A	intron	N/A	ENSP00000393638.2	P32780-1

Frequencies

GnomAD3 genomes

AF:

0.461

AC:

69886

AN:

151728

Hom.:

18501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.530

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.508

AC:

1424

AN:

2802

Hom.:

405

AF XY:

0.518

AC XY:

796

AN XY:

1536

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.486

AC:

102

AN:

210

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

AN:

East Asian (EAS)

AF:

0.722

AC:

AN:

South Asian (SAS)

AF:

0.466

AC:

108

AN:

232

European-Finnish (FIN)

AF:

0.515

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.521

AC:

1096

AN:

2104

Other (OTH)

AF:

0.418

AC:

AN:

110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.460

AC:

69910

AN:

151846

Hom.:

18504

Cov.:

AF XY:

0.463

AC XY:

34372

AN XY:

74168

show subpopulations

African (AFR)

AF:

0.196

AC:

8108

AN:

41458

American (AMR)

AF:

0.523

AC:

7968

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1475

AN:

3470

East Asian (EAS)

AF:

0.847

AC:

4368

AN:

5154

South Asian (SAS)

AF:

0.531

AC:

2553

AN:

4808

European-Finnish (FIN)

AF:

0.525

AC:

5519

AN:

10516

Middle Eastern (MID)

AF:

0.361

AC:

106

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38263

AN:

67902

Other (OTH)

AF:

0.446

AC:

939

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1694

3388

5082

6776

8470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

618

1236

1854

2472

3090

<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:

0.505

Hom.:

25179

Bravo

AF:

0.453

Asia WGS

AF:

0.656

AC:

2279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.60

(source)

DANN

Benign

0.29

PhyloP100

-0.081

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