rs879092890

Variant names:

• chr20-44355722-C-T
• rs879092890
• NM_175914.5:c.-83C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-44355722-C-T
• chr20-44355722-C-A
• chr20-44355722-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_175914.5(HNF4A):​c.-83C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.0000699 in 1,259,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (★★). The gene HNF4A is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000069 (0 hom.)
• Consequence: HNF4A NM_175914.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance/Uncertain risk allele criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 3.60
• Publications: 1 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]

R3HDML-AS1 (HGNC:55830): (R3HDML antisense RNA 1)

ACMG classification

Specifications for HNF4A are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BS2: High AC in GnomAd4 at 12 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4A	NM_175914.5	MANE Select	c.-83C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_787110.2
	HNF4A	NM_175914.5	MANE Select	c.-83C>T		5_prime_UTR	Exon 1 of 10	NP_787110.2
	HNF4A	NM_001287183.2		c.-314C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001274112.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HNF4A	ENST00000316673.9	TSL:1 MANE Select	c.-83C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000315180.4	P41235-5
	HNF4A	ENST00000316673.9	TSL:1 MANE Select	c.-83C>T		5_prime_UTR	Exon 1 of 10	ENSP00000315180.4	P41235-5
	HNF4A	ENST00000894460.1		c.-83C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000564519.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152236 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000686 AC: 76 AN: 1107558 Hom.: 0 Cov.: 15 AF XY: 0.0000688 AC XY: 39 AN XY: 566918

African (AFR) AF: 0.0000374 AC: 1 AN: 26720

American (AMR) AF: 0.000115 AC: 5 AN: 43374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23834

East Asian (EAS) AF: 0.00 AC: 0 AN: 37858

South Asian (SAS) AF: 0.00 AC: 0 AN: 78566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4340

European-Non Finnish (NFE) AF: 0.0000844 AC: 67 AN: 793914

Other (OTH) AF: 0.0000619 AC: 3 AN: 48448

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74370

African (AFR) AF: 0.0000241 AC: 1 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000756

ClinVar

ClinVar submissions

Significance: Uncertain significance/Uncertain risk allele

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Maturity-onset diabetes of the young (1)
-	1	-	Maturity-onset diabetes of the young type 1 (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.95
PhyloP100		3.6
PromoterAI		-0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=297/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs879092890; hg19: chr20-42984362;