dbSNP rs456396: GTF3C4:c.2404+86G>A (chr9-132687413-G-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_012204.4(GTF3C4):c.2404+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 672,278 control chromosomes in the GnomAD database, including 85,954 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 0.51 ( 17995 hom., cov: 24)

Exomes 𝑓: 0.53 ( 67959 hom. )

Consequence

GTF3C4
NM_012204.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.713

Publications

9 publications found

Variant links:

Genes affected

GTF3C4 (HGNC:4667): (general transcription factor IIIC subunit 4) Predicted to enable enzyme activator activity. Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and tRNA transcription by RNA polymerase III. Located in mitochondrion and nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C4 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=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012204.4. 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
	GTF3C4	NM_012204.4	MANE Select	c.2404+86G>A		intron	N/A	NP_036336.2	Q9UKN8
	GTF3C4	NR_133925.1		n.3006+86G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C4	ENST00000372146.5	TSL:1 MANE Select	c.2404+86G>A		intron	N/A	ENSP00000361219.4	Q9UKN8
	GTF3C4	ENST00000898845.1		c.640+86G>A		intron	N/A	ENSP00000568904.1

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

71814

AN:

141998

Hom.:

17967

Cov.:

show subpopulations

Gnomad AFR

AF:

0.638

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.363

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.482

Gnomad NFE

AF:

0.408

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.526

AC:

278834

AN:

530166

Hom.:

67959

AF XY:

0.516

AC XY:

148457

AN XY:

287972

show subpopulations

African (AFR)

AF:

0.671

AC:

11283

AN:

16826

American (AMR)

AF:

0.590

AC:

23616

AN:

40054

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

7151

AN:

15650

East Asian (EAS)

AF:

0.647

AC:

18676

AN:

28854

South Asian (SAS)

AF:

0.421

AC:

26604

AN:

63212

European-Finnish (FIN)

AF:

0.591

AC:

23577

AN:

39922

Middle Eastern (MID)

AF:

0.463

AC:

961

AN:

2074

European-Non Finnish (NFE)

AF:

0.514

AC:

152696

AN:

296924

Other (OTH)

AF:

0.535

AC:

14270

AN:

26650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.672

Heterozygous variant carriers

5016

10032

15047

20063

25079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1766

3532

5298

7064

8830

<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:

0.506

AC:

71896

AN:

142112

Hom.:

17995

Cov.:

AF XY:

0.518

AC XY:

35362

AN XY:

68302

show subpopulations

African (AFR)

AF:

0.638

AC:

25186

AN:

39452

American (AMR)

AF:

0.564

AC:

7471

AN:

13254

Ashkenazi Jewish (ASJ)

AF:

0.363

AC:

1214

AN:

3348

East Asian (EAS)

AF:

0.614

AC:

2896

AN:

4716

South Asian (SAS)

AF:

0.453

AC:

1907

AN:

4206

European-Finnish (FIN)

AF:

0.602

AC:

5379

AN:

8938

Middle Eastern (MID)

AF:

0.476

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.408

AC:

26594

AN:

65200

Other (OTH)

AF:

0.473

AC:

916

AN:

1936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.614

Heterozygous variant carriers

1647

3295

4942

6590

8237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<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:

0.417

Hom.:

37682

Bravo

AF:

0.485

Asia WGS

AF:

0.481

AC:

1671

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.14

(source)

DANN

Benign

0.55

PhyloP100

-0.71

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