20-44355529-G-T

Variant names:

• chr20-44355529-G-T
• rs148318607
• NM_175914.5:c.-276G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_175914.5(HNF4A):​c.-276G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 152,306 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 Benign (★★).

• Frequency: Genomes: 𝑓 0.0039 (0 hom., cov: 32)
• Consequence: HNF4A NM_175914.5 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.10

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 20-44355529-G-T is Benign according to our data. Variant chr20-44355529-G-T is described in ClinVar as [Benign]. Clinvar id is 435433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00392 (597/152306) while in subpopulation EAS AF= 0.0126 (65/5174). AF 95% confidence interval is 0.0101. There are 0 homozygotes in gnomad4. There are 294 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 597 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HNF4A	NM_175914.5	c.-276G>T		upstream_gene_variant		ENST00000316673.9	NP_787110.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HNF4A	ENST00000316673.9	c.-276G>T		upstream_gene_variant		1	NM_175914.5	ENSP00000315180.4

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00190

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.00392 AC: 597 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00395 AC XY: 294 AN XY: 74464

Gnomad4 AFR AF: 0.00565

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.0126

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00122

Gnomad4 NFE AF: 0.00190

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00359 Hom.: 0

Bravo AF: 0.00446

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

May 02, 2017

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.1
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs148318607; hg19: chr20-42984169;