17-37736525-C-T

Position:

• chr17-37736525-C-T

Variant summary

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

The NM_000458.4(HNF1B):​c.545-2704G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,974 control chromosomes in the GnomAD database, including 12,429 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 0.39 (12429 hom., cov: 31)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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 (Cadd=0.058).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.545-2704G>A		intron_variant		ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.545-2704G>A		intron_variant		1	NM_000458.4	ENSP00000480291
HNF1B	ENST00000613727.4	c.545-2782G>A		intron_variant		1		ENSP00000477524
HNF1B	ENST00000621123.4	c.545-2782G>A		intron_variant		1		ENSP00000482711	P1
HNF1B	ENST00000614313.4	c.545-2704G>A		intron_variant		5		ENSP00000482529

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59753 AN: 151856 Hom.: 12404 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.394 AC: 59813 AN: 151974 Hom.: 12429 Cov.: 31 AF XY: 0.386 AC XY: 28686 AN XY: 74302

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.394

Alfa AF: 0.367 Hom.: 15577

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
CADD	Benign	0.058

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs757210; hg19: -;