rs4239217

Positions:

• chr17-37738996-A-G

Variant summary

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

The NM_000458.4(HNF1B):​c.544+444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 152,118 control chromosomes in the GnomAD database, including 9,475 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 0.35 (9475 hom., cov: 32)
• Consequence: HNF1B NM_000458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

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 (NFE) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HNF1B	NM_000458.4	c.544+444T>C		intron_variant		ENST00000617811.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HNF1B	ENST00000617811.5	c.544+444T>C		intron_variant		1	NM_000458.4
HNF1B	ENST00000613727.4	c.544+444T>C		intron_variant		1
HNF1B	ENST00000621123.4	c.544+444T>C		intron_variant		1		P1
HNF1B	ENST00000614313.4	c.544+444T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52975 AN: 152000 Hom.: 9475 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.348 AC: 52974 AN: 152118 Hom.: 9475 Cov.: 32 AF XY: 0.343 AC XY: 25524 AN XY: 74364

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.354

Alfa AF: 0.378 Hom.: 6038

Bravo AF: 0.350

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4239217; hg19: chr17-36098987;