17-37686448-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000458.4(HNF1B):c.*924C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 151,952 control chromosomes in the GnomAD database, including 3,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3991 hom., cov: 31)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: HNF1B NM_000458.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.44

Genes affected

HNF1B (HGNC:11630): (HNF1 homeobox B) This gene encodes a member of the homeodomain-containing superfamily of transcription factors. The protein binds to DNA as either a homodimer, or a heterodimer with the related protein hepatocyte nuclear factor 1-alpha. The gene has been shown to function in nephron development, and regulates development of the embryonic pancreas. Mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 17-37686448-G-C is Benign according to our data. Variant chr17-37686448-G-C is described in ClinVar as [Benign]. Clinvar id is 322927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.*924C>G		3_prime_UTR_variant	9/9	ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.*924C>G		3_prime_UTR_variant	9/9	1	NM_000458.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33797 AN: 151812 Hom.: 3984 Cov.: 31

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.227 AC: 5 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.214 AC XY: 3 AN XY: 14

Gnomad4 NFE exome AF: 0.227

GnomAD4 genome AF: 0.223 AC: 33819 AN: 151930 Hom.: 3991 Cov.: 31 AF XY: 0.225 AC XY: 16730 AN XY: 74274

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.193

Alfa AF: 0.237 Hom.: 591

Bravo AF: 0.228

Asia WGS AF: 0.231 AC: 806 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal cysts and diabetes syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	11
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10962; hg19: chr17-36046451;