Genetic Variant HNF4G:c.383-52T>C (chr8-75551336-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004133.5(HNF4G):c.383-52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,014,188 control chromosomes in the GnomAD database, including 25,317 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 0.22 ( 3933 hom., cov: 31)

Exomes 𝑓: 0.22 ( 21384 hom. )

Consequence

HNF4G
NM_004133.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0210

Publications

6 publications found

Variant links:

Genes affected

HNF4G (HGNC:5026): (hepatocyte nuclear factor 4 gamma) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

HNF4G 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 = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004133.5. 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
	HNF4G	NM_004133.5	MANE Select	c.383-52T>C		intron	N/A	NP_004124.5
	HNF4G	NM_001330561.2		c.242-52T>C		intron	N/A	NP_001317490.1	Q14541-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF4G	ENST00000396423.4	TSL:1 MANE Select	c.383-52T>C	intron	N/A	ENSP00000379701.3	A0A6E1WB48
HNF4G	ENST00000354370.5	TSL:1	c.242-52T>C	intron	N/A	ENSP00000346339.1	Q14541-1
HNF4G	ENST00000674002.1		c.353-52T>C	intron	N/A	ENSP00000501146.1	Q14541-2

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33826

AN:

151750

Hom.:

3936

Cov.:

show subpopulations

Gnomad AFR

AF:

0.228

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.0958

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.357

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.228

GnomAD4 exome

AF:

0.215

AC:

185788

AN:

862318

Hom.:

21384

Cov.:

AF XY:

0.212

AC XY:

95482

AN XY:

450144

show subpopulations

African (AFR)

AF:

0.225

AC:

4758

AN:

21160

American (AMR)

AF:

0.190

AC:

7360

AN:

38724

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

4842

AN:

21180

East Asian (EAS)

AF:

0.117

AC:

4251

AN:

36294

South Asian (SAS)

AF:

0.124

AC:

8456

AN:

67990

European-Finnish (FIN)

AF:

0.339

AC:

17509

AN:

51622

Middle Eastern (MID)

AF:

0.276

AC:

1225

AN:

4442

European-Non Finnish (NFE)

AF:

0.221

AC:

128599

AN:

580782

Other (OTH)

AF:

0.219

AC:

8788

AN:

40124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

6817

13633

20450

27266

34083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3026

6052

9078

12104

15130

<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:

0.223

AC:

33837

AN:

151870

Hom.:

3933

Cov.:

AF XY:

0.225

AC XY:

16661

AN XY:

74206

show subpopulations

African (AFR)

AF:

0.227

AC:

9415

AN:

41416

American (AMR)

AF:

0.199

AC:

3040

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

791

AN:

3464

East Asian (EAS)

AF:

0.0962

AC:

496

AN:

5158

South Asian (SAS)

AF:

0.122

AC:

588

AN:

4818

European-Finnish (FIN)

AF:

0.357

AC:

3757

AN:

10522

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15046

AN:

67946

Other (OTH)

AF:

0.226

AC:

475

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1297

2594

3890

5187

6484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.220

Hom.:

5533

Bravo

AF:

0.213

Asia WGS

AF:

0.143

AC:

497

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

9.1

(source)

DANN

Benign

0.34

PhyloP100

0.021

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