rs3744763

Positions:

• chr17-37730894-A-G
• chr17-37730894-A-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+701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 155,150 control chromosomes in the GnomAD database, including 9,071 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 0.31 (8866 hom., cov: 32)
  • Exomes 𝑓: 0.33 (205 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNF1B	NM_000458.4	c.1045+701T>C		intron_variant		ENST00000617811.5	NP_000449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNF1B	ENST00000617811.5	c.1045+701T>C		intron_variant		1	NM_000458.4	ENSP00000480291

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47285 AN: 151964 Hom.: 8865 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.334 AC: 1024 AN: 3068 Hom.: 205 Cov.: 0 AF XY: 0.341 AC XY: 530 AN XY: 1554

Gnomad4 AFR exome AF: 0.0625

Gnomad4 AMR exome AF: 0.232

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.311 AC: 47271 AN: 152082 Hom.: 8866 Cov.: 32 AF XY: 0.309 AC XY: 22954 AN XY: 74318

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.545

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.309

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.340

Alfa AF: 0.389 Hom.: 7696

Bravo AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3744763; hg19: chr17-36090885;