chr20-44401844-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_175914.5(HNF4A):​c.50-4214A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00428 in 152,184 control chromosomes in the GnomAD database, including 7 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 0.0043 ( 7 hom., cov: 32)

Consequence

HNF4A
NM_175914.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.571

Publications

2 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 Gene-Disease associations (from GenCC):
  • maturity-onset diabetes of the young type 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • monogenic diabetes
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • diabetes mellitus, noninsulin-dependent
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
  • Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young
    Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
  • hyperinsulinism due to HNF4A deficiency
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • maturity-onset diabetes of the young
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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=-0.9).
BS1
Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00428 (651/152184) while in subpopulation EAS AF = 0.0346 (178/5150). AF 95% confidence interval is 0.0304. There are 7 homozygotes in GnomAd4. There are 319 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High AC in GnomAd4 at 651 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HNF4ANM_175914.5 linkc.50-4214A>T intron_variant Intron 1 of 9 ENST00000316673.9 NP_787110.2 P41235-5F1D8T0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HNF4AENST00000316673.9 linkc.50-4214A>T intron_variant Intron 1 of 9 1 NM_175914.5 ENSP00000315180.4 P41235-5

Frequencies

GnomAD3 genomes
AF:
0.00428
AC:
651
AN:
152066
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0102
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0349
Gnomad SAS
AF:
0.00414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00382
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.00428
AC:
651
AN:
152184
Hom.:
7
Cov.:
32
AF XY:
0.00429
AC XY:
319
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.0102
AC:
424
AN:
41524
American (AMR)
AF:
0.00118
AC:
18
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.0346
AC:
178
AN:
5150
South Asian (SAS)
AF:
0.00415
AC:
20
AN:
4822
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10602
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68012
Other (OTH)
AF:
0.00378
AC:
8
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
32
63
95
126
158
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00243
Hom.:
0
Bravo
AF:
0.00429
Asia WGS
AF:
0.0330
AC:
115
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.51
DANN
Benign
0.63
PhyloP100
-0.57
PromoterAI
0.028
Neutral
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs2071198; hg19: chr20-43030484; API