rs3110641

chr17-37687414-G-Achr17-37687414-G-Cchr17-37687414-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.1654-22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,583,410 control chromosomes in the GnomAD database, including 53,253 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 0.32 (9292 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43961 hom.)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.1654-22C>T		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.1654-22C>T		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.1262-22C>T		intron_variant		1
HNF1B	ENST00000621123.4	c.1576-22C>T		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.1535-22C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48501 AN: 151832 Hom.: 9261 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.239 AC: 342249 AN: 1431460 Hom.: 43961 Cov.: 26 AF XY: 0.242 AC XY: 172990 AN XY: 713878

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.197

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.211

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.264

GnomAD4 genome AF: 0.320 AC: 48588 AN: 151950 Hom.: 9292 Cov.: 32 AF XY: 0.318 AC XY: 23622 AN XY: 74256

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.324

Alfa AF: 0.258 Hom.: 6447

Bravo AF: 0.331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3110641; hg19: chr17-36047417;