rs6017341

Variant names:

• chr20-44434646-C-G
• rs6017341
• NM_001258355.2:c.*4981C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-44434646-C-G
• chr20-44434646-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001258355.2(HNF4A):​c.*4981C>G variant causes a downstream gene change. The variant allele was found at a frequency of 0.0749 in 152,220 control chromosomes in the GnomAD database, including 655 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 0.075 (655 hom., cov: 30)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: HNF4A NM_001258355.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.72
• Publications: 2 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 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• monogenic diabetes

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, G2P
• hyperinsulinism due to HNF4A deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001258355.2. 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_001258355.2		c.*4981C>G		downstream_gene	N/A	NP_001245284.1
	HNF4A	NM_178849.3		c.*4981C>G		downstream_gene	N/A	NP_849180.1
	HNF4A	NM_001030003.3		c.*4981C>G		downstream_gene	N/A	NP_001025174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11382 AN: 152010 Hom.: 654 Cov.: 30

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00905

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0160

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0721

GnomAD4 exome AF: 0.0109 AC: 1 AN: 92 Hom.: 0 Cov.: 0 AF XY: 0.0161 AC XY: 1 AN XY: 62

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0749 AC: 11400 AN: 152128 Hom.: 655 Cov.: 30 AF XY: 0.0714 AC XY: 5309 AN XY: 74374

African (AFR) AF: 0.160 AC: 6642 AN: 41454

American (AMR) AF: 0.106 AC: 1622 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0392 AC: 136 AN: 3470

East Asian (EAS) AF: 0.00888 AC: 46 AN: 5180

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4822

European-Finnish (FIN) AF: 0.0160 AC: 169 AN: 10586

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0366 AC: 2486 AN: 68016

Other (OTH) AF: 0.0714 AC: 151 AN: 2116

Alfa AF: 0.0188 Hom.: 14

Bravo AF: 0.0874

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		3.7

Splicing

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

Other links and lift over

dbSNP: rs6017341; hg19: chr20-43063286;