chr20-44395409-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_175914.5(HNF4A):​c.50-10649G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,334 control chromosomes in the GnomAD database, including 15,263 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 0.42 ( 15250 hom., cov: 33)
Exomes 𝑓: 0.50 ( 13 hom. )

Consequence

HNF4A
NM_175914.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170
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-AS1 (HGNC:49505): (HNF4A antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HNF4ANM_175914.5 linkuse as main transcriptc.50-10649G>T intron_variant ENST00000316673.9
HNF4A-AS1NR_172878.1 linkuse as main transcriptn.210+44C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HNF4AENST00000316673.9 linkuse as main transcriptc.50-10649G>T intron_variant 1 NM_175914.5 P41235-5
HNF4A-AS1ENST00000452481.1 linkuse as main transcriptn.254+44C>A intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.421
AC:
64102
AN:
152112
Hom.:
15239
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.186
Gnomad AMI
AF:
0.390
Gnomad AMR
AF:
0.577
Gnomad ASJ
AF:
0.438
Gnomad EAS
AF:
0.493
Gnomad SAS
AF:
0.357
Gnomad FIN
AF:
0.506
Gnomad MID
AF:
0.434
Gnomad NFE
AF:
0.515
Gnomad OTH
AF:
0.452
GnomAD4 exome
AF:
0.500
AC:
51
AN:
102
Hom.:
13
Cov.:
0
AF XY:
0.480
AC XY:
24
AN XY:
50
show subpopulations
Gnomad4 AFR exome
AF:
0.250
Gnomad4 AMR exome
AF:
0.833
Gnomad4 EAS exome
AF:
0.300
Gnomad4 FIN exome
AF:
0.600
Gnomad4 NFE exome
AF:
0.468
Gnomad4 OTH exome
AF:
0.750
GnomAD4 genome
AF:
0.421
AC:
64129
AN:
152232
Hom.:
15250
Cov.:
33
AF XY:
0.424
AC XY:
31528
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.186
Gnomad4 AMR
AF:
0.577
Gnomad4 ASJ
AF:
0.438
Gnomad4 EAS
AF:
0.493
Gnomad4 SAS
AF:
0.356
Gnomad4 FIN
AF:
0.506
Gnomad4 NFE
AF:
0.515
Gnomad4 OTH
AF:
0.452
Alfa
AF:
0.503
Hom.:
39062
Bravo
AF:
0.421
Asia WGS
AF:
0.408
AC:
1419
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
2.4
DANN
Benign
0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2425637; hg19: chr20-43024049; API