dbSNP rs6130608: HNF4A:c.50-10690T>C (chr20-44395368-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_175914.5(HNF4A):c.50-10690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,340 control chromosomes in the GnomAD database, including 8,706 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 0.33 ( 8700 hom., cov: 34)

Exomes 𝑓: 0.25 ( 6 hom. )

Consequence

HNF4A
NM_175914.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Publications

7 publications found

Variant links:

Genes affected

HNF4A (HGNC:5024): (hepatocyte nuclear factor 4 alpha) The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Apr 2012]

HNF4A links:

HNF4A-AS1 (HGNC:49505): (HNF4A antisense RNA 1)

HNF4A-AS1 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175914.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF4A	NM_175914.5	MANE Select	c.50-10690T>C	intron	N/A	NP_787110.2
HNF4A	NM_001287183.2		c.40+4689T>C	intron	N/A	NP_001274112.1
HNF4A	NM_001030003.3		c.50-10690T>C	intron	N/A	NP_001025174.1	P41235-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HNF4A	ENST00000316673.9	TSL:1 MANE Select	c.50-10690T>C	intron	N/A	ENSP00000315180.4	P41235-5
HNF4A	ENST00000457232.5	TSL:1	c.50-10690T>C	intron	N/A	ENSP00000396216.1	P41235-6
HNF4A	ENST00000609795.5	TSL:1	c.50-10690T>C	intron	N/A	ENSP00000476609.1	P41235-7

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49720

AN:

152108

Hom.:

8692

Cov.:

show subpopulations

Gnomad AFR

AF:

0.452

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.230

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.314

GnomAD4 exome

AF:

0.254

AC:

AN:

114

Hom.:

AF XY:

0.256

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.266

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.327

AC:

49754

AN:

152226

Hom.:

8700

Cov.:

AF XY:

0.328

AC XY:

24386

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.452

AC:

18782

AN:

41550

American (AMR)

AF:

0.229

AC:

3509

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1241

AN:

3468

East Asian (EAS)

AF:

0.317

AC:

1637

AN:

5170

South Asian (SAS)

AF:

0.430

AC:

2074

AN:

4828

European-Finnish (FIN)

AF:

0.259

AC:

2748

AN:

10600

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18524

AN:

67992

Other (OTH)

AF:

0.313

AC:

660

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1718

3435

5153

6870

8588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

490

980

1470

1960

2450

<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:

0.298

Hom.:

4381

Bravo

AF:

0.323

Asia WGS

AF:

0.355

AC:

1235

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

(source)

DANN

Benign

0.68

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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