rs1016990

chr17-37728924-G-Cchr17-37728924-G-T

Variant summary

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

The NM_000458.4(HNF1B):c.1045+2671C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 154,426 control chromosomes in the GnomAD database, including 6,568 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 0.27 (6452 hom., cov: 31)
  • Exomes 𝑓: 0.31 (116 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.959

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.1045+2671C>G		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.1045+2671C>G		intron_variant		1	NM_000458.4

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41308 AN: 152032 Hom.: 6448 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.300

GnomAD4 exome AF: 0.311 AC: 708 AN: 2274 Hom.: 116 Cov.: 0 AF XY: 0.286 AC XY: 360 AN XY: 1260

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.259

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.272 AC: 41314 AN: 152152 Hom.: 6452 Cov.: 31 AF XY: 0.268 AC XY: 19959 AN XY: 74384

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.297

Alfa AF: 0.180 Hom.: 392

Bravo AF: 0.267

Asia WGS AF: 0.290 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.5
Dann	Benign	0.58

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: rs1016990; hg19: chr17-36088915;