rs6093976

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000316673.9(HNF4A):​c.225-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,202 control chromosomes in the GnomAD database, including 1,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1641 hom., cov: 32)

Consequence

HNF4A
ENST00000316673.9 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.944
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 20-44407140-C-T is Benign according to our data. Variant chr20-44407140-C-T is described in ClinVar as [Benign]. Clinvar id is 1235855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HNF4ANM_175914.5 linkuse as main transcriptc.225-241C>T intron_variant ENST00000316673.9 NP_787110.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HNF4AENST00000316673.9 linkuse as main transcriptc.225-241C>T intron_variant 1 NM_175914.5 ENSP00000315180 P41235-5

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19693
AN:
152084
Hom.:
1639
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0319
Gnomad AMI
AF:
0.371
Gnomad AMR
AF:
0.106
Gnomad ASJ
AF:
0.277
Gnomad EAS
AF:
0.170
Gnomad SAS
AF:
0.211
Gnomad FIN
AF:
0.134
Gnomad MID
AF:
0.253
Gnomad NFE
AF:
0.173
Gnomad OTH
AF:
0.147
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.129
AC:
19693
AN:
152202
Hom.:
1641
Cov.:
32
AF XY:
0.130
AC XY:
9652
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.0319
Gnomad4 AMR
AF:
0.106
Gnomad4 ASJ
AF:
0.277
Gnomad4 EAS
AF:
0.170
Gnomad4 SAS
AF:
0.210
Gnomad4 FIN
AF:
0.134
Gnomad4 NFE
AF:
0.173
Gnomad4 OTH
AF:
0.152
Alfa
AF:
0.165
Hom.:
1092
Bravo
AF:
0.123
Asia WGS
AF:
0.191
AC:
666
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.50
DANN
Benign
0.52

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

LitVar

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

Other links and lift over

dbSNP: rs6093976; hg19: chr20-43035780; API