rs6073418

chr20-44371950-C-T

Variant summary

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

The NM_175914.5(HNF4A):c.49+16097C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,098 control chromosomes in the GnomAD database, including 9,583 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 0.35 (9583 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF4A	NM_175914.5	c.49+16097C>T		intron_variant		ENST00000316673.9
HNF4A-AS1	NR_172878.1	n.361-11029G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF4A	ENST00000316673.9	c.49+16097C>T		intron_variant		1	NM_175914.5
HNF4A	ENST00000457232.5	c.49+16097C>T		intron_variant		1
HNF4A	ENST00000609262.5	c.-183+16097C>T		intron_variant		1
HNF4A	ENST00000609795.5	c.49+16097C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53449 AN: 151978 Hom.: 9577 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.352 AC: 53480 AN: 152098 Hom.: 9583 Cov.: 32 AF XY: 0.349 AC XY: 25941 AN XY: 74348

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.341

Alfa AF: 0.349 Hom.: 7361

Bravo AF: 0.345

Asia WGS AF: 0.363 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.4
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6073418; hg19: chr20-43000590;