17-37686928-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000458.4(HNF1B):c.*444A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 334,674 control chromosomes in the GnomAD database, including 28,935 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 0.42 (13215 hom., cov: 32)
  • Exomes 𝑓: 0.41 (15720 hom.)
• Consequence: HNF1B NM_000458.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.*444A>C		3_prime_UTR_variant	9/9	ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.*444A>C		3_prime_UTR_variant	9/9	1	NM_000458.4

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63056 AN: 151858 Hom.: 13201 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.398

GnomAD4 exome AF: 0.406 AC: 74213 AN: 182698 Hom.: 15720 Cov.: 0 AF XY: 0.407 AC XY: 39198 AN XY: 96202

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.422

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.415 AC: 63113 AN: 151976 Hom.: 13215 Cov.: 32 AF XY: 0.417 AC XY: 30997 AN XY: 74286

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.391

Gnomad4 OTH AF: 0.399

Alfa AF: 0.389 Hom.: 17018

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2688; hg19: chr17-36046931;