20-44356715-A-G

Variant names:

• chr20-44356715-A-G
• rs6031546
• NM_175914.5:c.49+862A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175914.5(HNF4A):​c.49+862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,220 control chromosomes in the GnomAD database, including 2,760 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 (2760 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 10 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4A	NM_175914.5	MANE Select	c.49+862A>G		intron	N/A	NP_787110.2
	HNF4A	NM_001287183.2		c.-183+862A>G		intron	N/A	NP_001274112.1
	HNF4A	NM_001030003.3		c.49+862A>G		intron	N/A	NP_001025174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4A	ENST00000316673.9	TSL:1 MANE Select	c.49+862A>G		intron	N/A	ENSP00000315180.4
	HNF4A	ENST00000457232.5	TSL:1	c.49+862A>G		intron	N/A	ENSP00000396216.1
	HNF4A	ENST00000609795.5	TSL:1	c.49+862A>G		intron	N/A	ENSP00000476609.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28260 AN: 152102 Hom.: 2761 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.186 AC: 28258 AN: 152220 Hom.: 2760 Cov.: 32 AF XY: 0.182 AC XY: 13572 AN XY: 74414

African (AFR) AF: 0.147 AC: 6121 AN: 41530

American (AMR) AF: 0.143 AC: 2182 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 868 AN: 3470

East Asian (EAS) AF: 0.131 AC: 679 AN: 5176

South Asian (SAS) AF: 0.135 AC: 650 AN: 4824

European-Finnish (FIN) AF: 0.202 AC: 2141 AN: 10610

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.219 AC: 14860 AN: 67986

Other (OTH) AF: 0.177 AC: 373 AN: 2112

Alfa AF: 0.210 Hom.: 13597

Bravo AF: 0.182

Asia WGS AF: 0.125 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.28
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6031546; hg19: chr20-42985355;