rs2144908

Positions:

• chr20-44357077-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175914.5(HNF4A):​c.49+1224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,064 control chromosomes in the GnomAD database, including 3,529 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 0.19 (3529 hom., cov: 31)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.49+1224G>A		intron_variant		ENST00000316673.9	NP_787110.2
HNF4A-AS1	NR_172878.1	n.4205C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.49+1224G>A		intron_variant		1	NM_175914.5	ENSP00000315180
HNF4A	ENST00000457232.5	c.49+1224G>A		intron_variant		1		ENSP00000396216
HNF4A	ENST00000609262.5	c.-183+1224G>A		intron_variant		1		ENSP00000476310
HNF4A	ENST00000609795.5	c.49+1224G>A		intron_variant		1		ENSP00000476609

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28867 AN: 151946 Hom.: 3511 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.210

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28913 AN: 152064 Hom.: 3529 Cov.: 31 AF XY: 0.199 AC XY: 14772 AN XY: 74298

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.210

Alfa AF: 0.183 Hom.: 4644

Bravo AF: 0.201

Asia WGS AF: 0.363 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2144908; hg19: chr20-42985717;