chr20-44371950-C-T

Variant names:

• chr20-44371950-C-T
• rs6073418
• NM_175914.5:c.49+16097C>T

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+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
• Publications: 15 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=-0.89).
• 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 rank	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.49+16097C>T		intron_variant	Intron 1 of 9	ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.49+16097C>T		intron_variant	Intron 1 of 9	1	NM_175914.5	ENSP00000315180.4

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

African (AFR) AF: 0.380 AC: 15752 AN: 41490

American (AMR) AF: 0.275 AC: 4199 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3466

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5166

South Asian (SAS) AF: 0.414 AC: 1994 AN: 4818

European-Finnish (FIN) AF: 0.333 AC: 3521 AN: 10576

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24081 AN: 67992

Other (OTH) AF: 0.341 AC: 720 AN: 2110

Alfa AF: 0.348 Hom.: 10097

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
PhyloP100		-0.21
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: rs6073418; hg19: chr20-43000590;