Genetic Variant NM_004133.5:c.*65G>A (chr8-75564161-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004133.5(HNF4G):c.*65G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,562,848 control chromosomes in the GnomAD database, including 185,180 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 0.53 ( 22910 hom., cov: 33)

Exomes 𝑓: 0.48 ( 162270 hom. )

Consequence

HNF4G
NM_004133.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.27

Publications

16 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4G	NM_004133.5 link	c.*65G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000396423.4	NP_004124.5	Q14541F1D8Q4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HNF4G	ENST00000396423.4 link	c.*65G>A	3_prime_UTR_variant	Exon 10 of 10	1	NM_004133.5	ENSP00000379701.3	A0A6E1WB48
HNF4G	ENST00000354370.5 link	c.*65G>A	3_prime_UTR_variant	Exon 11 of 11	1		ENSP00000346339.1	Q14541-1
HNF4G	ENST00000674002.1 link	c.*65G>A	3_prime_UTR_variant	Exon 10 of 10			ENSP00000501146.1	Q14541-2

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81300

AN:

152010

Hom.:

22887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.720

Gnomad AMI

AF:

0.559

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.444

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.422

Gnomad FIN

AF:

0.557

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.512

GnomAD4 exome

AF:

0.475

AC:

670265

AN:

1410720

Hom.:

162270

Cov.:

AF XY:

0.474

AC XY:

332673

AN XY:

702458

show subpopulations

African (AFR)

AF:

0.729

AC:

23706

AN:

32520

American (AMR)

AF:

0.309

AC:

13231

AN:

42850

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

10967

AN:

24694

East Asian (EAS)

AF:

0.393

AC:

15386

AN:

39178

South Asian (SAS)

AF:

0.416

AC:

34399

AN:

82618

European-Finnish (FIN)

AF:

0.549

AC:

27074

AN:

49334

Middle Eastern (MID)

AF:

0.435

AC:

2430

AN:

5590

European-Non Finnish (NFE)

AF:

0.479

AC:

515556

AN:

1075342

Other (OTH)

AF:

0.470

AC:

27516

AN:

58594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

16129

32258

48387

64516

80645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15146

30292

45438

60584

75730

<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:

0.535

AC:

81370

AN:

152128

Hom.:

22910

Cov.:

AF XY:

0.532

AC XY:

39526

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.720

AC:

29907

AN:

41518

American (AMR)

AF:

0.394

AC:

6018

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.444

AC:

1541

AN:

3472

East Asian (EAS)

AF:

0.348

AC:

1800

AN:

5170

South Asian (SAS)

AF:

0.420

AC:

2028

AN:

4826

European-Finnish (FIN)

AF:

0.557

AC:

5897

AN:

10584

Middle Eastern (MID)

AF:

0.435

AC:

127

AN:

292

European-Non Finnish (NFE)

AF:

0.478

AC:

32464

AN:

67968

Other (OTH)

AF:

0.511

AC:

1080

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1888

3776

5664

7552

9440

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.485

Hom.:

31195

Bravo

AF:

0.527

Asia WGS

AF:

0.395

AC:

1370

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

3.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over